Good morning everyone.
Thank you so much for joining us here today on the Rey Juan Carlos University
campus. For many of you, this will surely be your first contact with the
university, and specifically with this institution, Rey Juan Carlos
University. We hope this experience is very pleasant and that we will soon
be here in these classrooms and on this campus. Between us, in this great
university family, the reason we are gathered here today is twofold.
On the one hand, we want to celebrate in a very special way the closing
of the third edition of Micromundo RJ C in which many of us here today
have participated in one way or another. To the teachers who have been
involved in this Service-Learning project, we want to thank you for
the enthusiasm you have put into this activity and we hope to continue counting
on your help.
For many editions.
On the other hand, the second reason for this event is to celebrate the first
edition of the Awareness Day on the silent pandemic caused by
multi-resistance to antimicrobials.
The motto We are JC.
This initiative has been organized by a group from the High Performance Research
Group in Biotechnology and Ecology for Global Change at Rey Juan Carlos
University.
I co-CG, together with the research professors of the Institute for
Research Technologies for Sustainability at this University.
With this conference, which we hope will continue for many years, we intend
to bring together leading experts in the field of antimicrobial
resistance, covering both its basic and more applied aspects.
The day has a clear objective: to focus on resistance to antibiotics and
antifungals, an increasingly relevant problem globally, but one that still
does not receive the attention it deserves outside of the scientific field.
To achieve this, we have designed a program that combines outreach, science,
and debate.
Throughout the day we will be giving the floor to experts from different
institutions who
will provide complementary views on the problem of antimicrobial resistance.
After the first three presentations, we will take a short break where we can
enjoy coffee, soft drinks, and sweet and savory snacks, courtesy of the organizing
team of these sessions.
After this coffee break we will have three more presentations and an
interactive session
led by the group of experts from the National Plan against antimicrobial
resistance.
To conclude the day, we will offer the possibility of visiting two of the
research facilities available at the UMH Technological Support Center, CJC.
The organism cultivation laboratory, cultivation,
crops and the water treatment plant.
Well, as Sergio said, with this first edition, which we
hope will be many more, we intend to create a meeting
place between microbiology and public health.
It also aims to give greater visibility to microbiology within the
Rey Juan Carlos University and to help antibiotic resistance cease
to be a silent pandemic and become an increasingly
well-known and understood issue in society.
And so, from the organization we wanted to give a huge
thank you to all the attendees and especially to the
speakers who made time in their busy schedules to come
here and share their research, ideas and knowledge.
So, let's move on to the presenters of the talks.
Thank you.
Hey! It's a pleasure to start this day with Dr. Jessica Gil Serna,
Professor of Microbiology at the Complutense University of Madrid.
Throughout his career he has stood out for his commitment to
scientific dissemination and educational innovation.
EH leading initiatives that connect research with society.
His research focuses on agri-food microbiology and
mycology applied to the study, detection and control
of fungi, ethnic mycotoxins and mycotoxins in agri-food systems.
It is one of the world's leading promoters with an already consolidated
impact both nationally and internationally, and its work has been
recognized for its contribution to raising awareness about
antimicrobial resistance and involves fostering vocations among young people.
Today he's going to introduce us to microworlds.
Ten years of citizen science to protect the future of antimicrobials.
Thank you so much for the presentation and thank you so much for the invitation.
It's always a pleasure to be in this forum and be able to talk about the
microworld.
I know many of you have already participated in Microworld, so perhaps
what I'm going to
tell you here today isn't something that will be completely new to you.
But hey, it's always good to dedicate a little time to
reflecting on the importance of this project and everything
we have managed to accomplish in these ten years of the project.
Okay, this is a good introduction, and then we'll see if I can get this done.
I know that there are people who are really experts on this subject
who will give us a lot of information about antimicrobial resistance.
But what I want to tell you is that this is not something new; it is
something we have known for a very long time that has been happening.
For example, when Fleming was awarded the Nobel Prize
for the discovery of penicillin, he warned us that this
could happen, that bacteria or microorganisms in
general could learn to resist these treatments.
What Fleming was referring to was the possibility that there could
be ignorant men who overused antibiotics, and that this could make
it so that these bacteria could no longer be treated with those antibiotics.
But it is true that there is something that marked a turning point,
which is in 2016 when what we know as the Onil report was published,
which gave us a series of data that really frightened us a bit,
especially the politicians, who are the ones who have to put money
into this so that it can be done, so that research can be done in this field and
progress can be made.
The Onil report told us that if we did nothing, by 2050
we would have more deaths due to infections caused by
antimicrobial-resistant microorganisms than from cancer.
That was something that really caught our attention, and that's
when the idea that we had to do something was kind of raised.
Currently, even though this report was published
ten years ago, it's still something we continue to
use and try to ensure that this never happens, that
it doesn't happen in 2050. So, we could say that from
this point on, even though we already knew it was a
problem, we began to dedicate a series of efforts to try to stop it.
And here a project emerged, which is the
initiative that started in Wisconsin.
Thanks to this, to this microbiology professor, Joan
Altman, who realized that it was essential to involve
society, in this case university students, to try to
solve this problem using a strategy in which she involved
university students in the discovery of new antibiotics.
This initiative, as I said, is a little different.
The university in the United States, compared to what it is here, was not a
subject in a degree program.
If you don't know, there's a kind of series of courses that university
students can take, and what I was trying to do was use
this strategy to discover new antimicrobials.
It was also partly to encourage students to
pursue science degrees, and Joan Elfman wanted
this initiative strategy to spread throughout
the United States, but also throughout the world.
So what I did was a series of training sessions for people who
wanted to bring this strategy to their universities.
And this is where Micromundo arrives in Spain.
We used to call it the initiative, then we changed the name and it was thanks
to Professor Víctor Jiménez Cid who coordinates, coordinates
this project with me at the Complutense University.
Micromundo is coming to Spain, but what we wanted
here was to give this project a little twist.
Furthermore, the birth of Micromundo was very funny because when Victor came
back from doing that wonderful course in Wisconsin about the initiative,
what he thought was I can't do this alone, I have to find people who want to
get involved in this.
And then one day we suddenly received a very random email saying they
wanted microbiology professors who wanted to raise awareness about
antimicrobial resistance by embarking on this project, and to be
honest, with a bit of fear, a few of us got together and started.
We started there. This, this project.
Furthermore, in the birth of Micromundo, I wanted, as you know,
to delve deeper into what we call those strategies or angels.
We will never be able to stop the strategy.
If we focus solely on human health, we need to bring together a large
number of professionals to implement this strategy for antimicrobials.
Juan, health isn't just ours, it's very much ours.
We usually think we are the center of the universe, but that's not the case.
So we have to keep in mind that human health depends a lot
on environmental health and animal health.
So Micromundo emerged as a union between different faculties,
different faculties such as the Faculty of Biology, the Faculty
of Veterinary Medicine and the Faculty of Pharmacy.
Thus, in 2016, the Microworld project emerged, with a series
of objectives that have not changed since the beginning.
What the different policies tell us about what needs to be
done to end this problem is fundamentally based on four pillars.
There you have them: education, research, surveillance, and action.
Well, in the case of Micromundo we are going to face two or we are going to use
two of those pillars.
We are going to try to educate society about this problem,
but we are also going to do research to collaborate
in the discovery of new antimicrobials.
So we were very clear about it from the beginning, we were very clear about it.
Those of you who have participated already know what Micromundo wants.
The first step is to disseminate scientific culture.
We want to raise awareness among the population that this is a problem, and
also to help them understand that we are starting from the premise that people
may not be very clear about the concept of infectious diseases.
The concept of angels, we have to make this
society able to understand all these aspects
so that we can all work together.
But MicroMundos also wants to generate scientific vocations.
Everyone who's out there has already participated in Microworld.
As you know, one of the things is that we want to get involved
in a real experiment, because we really do need scientists.
In this world, vocations are declining; science is
getting that, let's say, rumor, which is partly true,
that it's a very difficult career, but we need young
people who are eager to do research to address problems,
especially these global health problems that affect us all.
But well, this would be the general goal regarding awareness, to create scientific
vocations.
But you already know that Micromundo is also a citizen
science project because we are very clear that tinkering,
using, and being involved in a real process makes
this awareness process much more effective.
So what we're going to do is involve a lot of
young scientists in their schools to discover,
or try to discover, new antimicrobial compounds.
We think that's one of the nicest things about Microworld.
But if all this were not enough, you can see that Micromundo is not a project, it
is not a simple project.
Furthermore, it is a Service-Learning project because we don't want to be.
As a university professor, I am not the one who goes to
high schools to teach people how to do a series of
experiments and discover new antibiotics; rather,
it is the university students who go to those educational
centers to lead that awareness-raising work.
So it's a Service-Learning project because we're going to do a
service to the community with all this that we've talked about,
that awareness, that generation of scientific culture in society,
but also our university students are going to learn, learn many things.
Many times, practically every year, people tell me when we're going to do
a microworld, that they didn't think being teachers was so difficult or
about all the organizational work and everything that needs to be prepared.
So they learn the first thing to disseminate.
We're going to explain very complex concepts to people who don't know
much about them yet, but we'll also be doing organizational tasks related
to teaching and all that. So, besides being a citizen science
project, it's also a service-learning project.
And many of you also know how we work.
I say Micromundo, I say it with all my heart, with all my love always.
But Micromundo is a bit of a cult because we have a pyramid structure.
Look, we're going to have a university professor who
will work with a group of about five university students
and they will go to a high school to do that research work
in order to try to discover new antibiotics.
So we work with this structure that allows us to
work with students at the institute, so we can
analyze a lot of samples with our citizen science project.
Then we'll look at the data a bit because everything Micromundo has achieved
is truly overwhelming, and it's also a bit of a cult, I tell you, I say it with
all
due respect, because normally when a person participates in Micromundo they
get so hooked in schools that they ask us again, "Please come back
another year to do that," as do the teachers themselves.
I am motivated. I have been here for ten years continuing to do
Micromundo every year, but also our university students who like
Micromundo and want to continue participating every year they are at
university.
So this is a bit of the organization we have, and this
organization allows us to have such beautiful images
as these very young university professors who are studying.
In the case of the Faculty of Biology, for example, we have students
between the third year of undergraduate studies and the first year of master's
studies.
They are the ones who will participate there, so a very nice collaboration
is established with the high school students, because in
the end that gap, they are only a few years apart.
It's like they're kind of working among friends, and
we have a lot of high school students who are going
to get involved in that real experiment.
On the first day we're going to do four sessions at Micromundo. On the
first day we're going to do those awareness talks about the importance
of antimicrobial resistance, we're going to talk to them about
Micromundo and we're also going to give them a kit so they can go and take a soil
sample wherever they want.
What we want is for all the students to be very original, going to
places never explored, where no one has ever seen the diversity
of those soils, and the soil is selected because it is one of the
places where we have the most microorganisms and we know that there is
a lot of competition.
As you know, microorganisms don't produce antibiotics for us;
that's just something we say, "well," they produce antibiotics for us humans to
use.
That's not the case.
They usually use it to carve out a niche for themselves, to carve out a niche in
that environment.
So all the high school students are going to go and
get a soil sample wherever they like or
whatever sample they want to analyze.
The second one: Oops, I've used the wrong arrow.
On the second day, what we're going to do is isolate those bacteria from the soil.
Let's do it.
I really like this day because it's a practice we also do at university.
We do it in microbiology practicals; I always tell my second-year
students that they do it much better at the institute than they do.
I don't know if it's because you're much more focused, or because you're
much more keen, which is something very different, but it's a
practice that is not easy at an experimental level.
It works wonderfully in schools, and that's where we have our first "Wow"
moments!
When we arrive and have those plates, microbiology is a
field that is, well, a very challenging one.
Disseminating information in the field of microbiology is a significant
challenge, because we are talking about things that cannot be seen.
These are super abstract things, but the first day we arrive with
the plates and we can see, the students see that we can indeed see
the soil bacteria that have grown in the culture media.
Well, that's something that's always in style.
Those "wow" moments when we see them are something very beautiful,
and from these microorganisms that we have managed to isolate,
what we are going to do is check if they are capable of producing those
antibiotic compounds, and for that we are going to use some bacteria
that we call escape bacteria, and escape bacteria are the ones that
are being researched the most because they are multi-resistant
bacteria associated with hospital infections.
They have a very serious problem that I'm sure we'll hear a lot about today.
Of course, we can't bring escaped bacteria into a school, so what we're
bringing are the cousins ​​of these bacteria, and we're going to test,
through some simple experiments, whether these bacteria are capable
of producing compounds that will inhibit our bacteria.
When we get to the 4th day, we're going to see if we can say
that these bacteria actually produce antibiotics,
and here we call it the Eureka moment, because everyone
gets very happy and it's the most beautiful day at the
institute, because we start to see our growth inhibition
on those plates and from here on out, the microworld at the institute ends.
But we're trying to leave that mark, aren't we?
We hope that everything we have done may be
useful both for high school students and,
who knows, perhaps for science at some point.
And this is what we do, many of you have already participated
in it, and as I mentioned, the Microworld project started
at the Complutense University and we have evolved a lot.
We started in 2016 and as you can see, we are increasingly able
to involve more university students in visiting more centers.
It depends a lot.
We would love to visit.
We have 150 centers that are interested in this, but we can't reach any more.
We would love to, but... But so you see, it's just like a Pokémon evolution,
the Microworld evolution at the Complutense University.
And if you've done a little calculation and connected the dots
with the title of my talk, you can imagine that Micromundo, since
it arrived in Spain, is celebrating its anniversary because we're
turning ten years old doing this beautiful project.
Not even the pandemic could stop us.
It is true that we were unable to make those in-person visits to the schools,
but we hope that...
But we made a lot of material, we made online games, infographics, a
lot of things that are available and you can have them if you are interested.
And here I want to tell you that this "long live microworld" thing was
coined by the journalists of the Scientific Culture Unit of the
Complutense University and I love it, so I use it.
But what I want, what is one of the things that excites
us most at Micromundo UCM, is that we don't stay at UCM.
We have been fortunate enough to be able to extend microworld
to many other universities, and that is why we are here today.
Because look, we started in 2016 and a lot of universities have joined,
not only from Spain, we also have, we call it the Iberian Microworld
Network, because there are also universities in Portugal that are working
on this.
If you find each other, you're down here.
In 2023, the Rey Juan Carlos University joined this
project, and the truth is that for us it is exciting to
see how this project grows and that there are so many
universities that are interested in doing it.
So, since the Micromundo project had grown so much a
couple of years ago, we wondered if we had really made
an impact, if we had achieved our goals,
and if what we were doing was worthwhile.
So we started doing a lot of calculations, asking universities,
"Hey, what have you done, how much have you done?"
And we didn't get the results we wanted.
The results we obtained were so overwhelming that we decided to make a
publication.
Because?
Can't you imagine? Now I'll tell you.
Everything Micromundo had achieved in eight years.
Okay, this does it.
It was in the year 2023, so let's hope it's in a few days.
Given that more universities are joining in a couple of years, we can recap all of
this.
But look at this one.
If you're curious, here's the article.
But look closely, okay?
In eight years the Micromundo Ibérica community
had managed to analyze more than 9500 soil samples.
This is outrageous if we think about laboratories; doing that
with a research group would be extremely complicated.
We have involved or are involving more than 18,000 high
school students who have analyzed more than 145,000 microorganisms.
Okay, the results are, as I said, they were super surprising to us.
Of all that we have analyzed, we found a positive
antibiotic in 6244, which corresponds to approximately
4% of the microorganisms we have analyzed.
It is true that that 4% is most likely due to microorganisms
that produce antibiotics that we already know.
Okay, there are many soil bacteria that we have already characterized many
times and we know what they produce, but it is true that this is where we have our
bottleneck.
We have a lot of potentially antibiotic-producing
microorganisms, but we are not capable.
I already said in the presentation, I work with fungi of food interest.
My research topic is not antimicrobials, but it
is true that some of the groups participating
in Micromundo do focus on this.
So look, Micromundo has already taken its first,
its first steps in the discovery of new
compounds that could be used at some point.
This 2024 article described a compound isolated from a
bacterium in the microworld, which was a bacterium or a cin,
but which is effective in treating certain bacteria.
If you see it, it's there.
It's very nice to read, to read that material and methods because
they mention, they mention the person or the student in this case
who isolated this bacteria and who started or could have started this.
This research is one.
It is a bacterium that is isolated from a bacterium that is
Bacillus altitud Inis and they called it SC 22.
You have it there because it says so.
EC starts with the center where it was isolated, which was the
Izal center in Madrid, and the other C is for Carlota, who is
the student who was able to isolate this bacteria
during her participation in Micromundo.
It's still in high school, but this year we're going
to have another article very soon related to another
Micromundo bacteria, so little by little Micromundo
is making those advances or we're achieving those
advances in research that we'd also like to share.
So, to conclude and to reflect effectively with
Micromundo on everything we do at all levels, we manage to help raise
awareness.
Furthermore, the.
We really like the group of high school students because we know
you are a voice, because when you leave creating a microworld you
will tell your friends, your parents, your families. And that is
very important for this awareness-raising work.
We need to get that message to the entire population,
but we are also trying to make progress in that research work.
We are able to analyze a large number of microorganisms and it is
true that we are going step by step, but we are achieving some
things and above all to promote those scientific
vocations which, I repeat, is super important.
For example, it's bound to happen to you, if it hasn't happened to you yet, it
will.
When I'm in my class, I teach microbiology to second-year
biology students and some students come up to me and tell me that
they did a microworld project at their high school and that it
helped them decide to study biology in this case.
So for us that's super important
and it really fills us with pride.
But the best thing about this whole project is not the
awareness, it's not the research, but how excited we all
are, the teachers, the students at the institute, when
we hold events like this, we come here, we collect diplomas.
So what I want to say to end my talk is that we should continue
to maintain that enthusiasm and never lose that motto of long live Micromundo.
And of course, thank you to everyone who participates, those who have
participated and those who are participating in this project.
Thank you so much.
Well, next we continue with Jerónimo Beltrán,
senior researcher at the Ramón y Cajal Institute
for Health Research, who has a solid track record
in biomedical research, participating in numerous
competitive projects both nationally and internationally.
His work focuses on the evolutionary biology of microorganisms
and the dynamics of antibiotic resistance, especially on
mechanisms of horizontal gene transfer and bacterial evolution.
His research contributes to understanding how resistance arises and spreads.
A key aspect to addressing this global challenge.
Today she joins us to share her experience and her vision on current
challenges in health research.
Thank you so much.
Well, thank you all very much for being here and especially
for inviting me to share some of my ideas, as
my presenter said, who did a great job.
Well, I'm a researcher.
Basically, I dedicate myself to researching and trying to
understand how the evolution of antimicrobial resistance works.
I do this at the Ramón y Cajal Hospital in Madrid.
And well, uh, throughout my career that's basically what I've dedicated myself to
all these years.
And well, today I'm going to talk a little bit about, as I was saying, these
ideas I have, about how we got to this problem of the silent pandemic, as
these conferences are called, and also about some possibilities we have
apart from the use of antibiotics, or in some way rethinking how we can tackle
this problem.
Through alternative mechanisms.
These are new strategies that we are trying to develop in the laboratory.
So I wanted to begin.
To that job.
Uh, I wanted to start this presentation with this image which, for
those of you who don't know, is Darwin asking for silence.
And I think it's a very beautiful image because it exemplifies very well how
evolution, and in particular the evolution of antimicrobial resistance,
has silenced all our efforts to end infectious diseases.
And this is because antimicrobial resistance is nothing more than an
evolutionary problem.
It is a problem that arises, at least in theory, from the natural evolution of all
organisms.
Bacteria, like all other organisms, adapt, change, and get
used to the environment in which they live, right?
And this is so, as I say, for all organisms, from whales, humans and of
course bacteria.
And also the finches, which are the ones that inspired
Charles Darwin to propose the theory of evolution.
And in the case of resistance, antibiotics.
This happens in a kind of vicious circle that I'm going to tell you
about now. Back in 1900, well, in the 1930s, the first antibiotics
began to be marketed, penicillin, which Fleming discovered,
as you all know. This meant that bacteria had to change, they had
to adapt to the presence of penicillin in the places where they
were going to cause infections, and so on. And that generated an
evolution, and the evolution of resistance meant that infectious
diseases that could previously be treated very easily with
penicillin became increasingly common.
Well, before we had diseases that couldn't be cured.
Penicillin appeared, now we can cure them.
Everyone was very happy, but suddenly the evolution of resistance made this no
longer possible.
Then, suddenly, penicillin stops working.
This creates a serious health problem, which is what we find ourselves
in today, and it means that society has to develop new antibiotics,
which is somewhat what all of you who have participated in micromundo
have been working on, trying to find new antibiotics to be able to tip
the scales back in our favor and give this circle another turn.
But this is somehow a...
It is an inevitable consequence of antibiotic use.
Resistant bacteria will always emerge.
So, we have been in this vicious circle for practically 100 years
since the massive introduction of the use of antibiotics.
Going around in this vicious circle a bit, and calling it a vicious
circle is what it's normally called, but in evolution we call it a Red Queen
dynamic.
I don't know if you know this, but the Red Queen is a character from the story
Alice in Wonderland, and in that story, which is a story by Louis Carroll,
what happens is that Alice travels through different places, all of them
very fantastical, and at a certain point she encounters this character
who is the Red Queen, and in the place where the Red Queen is in that country,
what happens is that, as the Red Queen explains to her, you
have to run as fast as you can to stay in the same place.
And if you wanted to run, if you wanted to go further, you would have to run at
least twice as fast.
Well, this is somewhat what happens with antibiotic resistance.
We're running as fast as we can, but simply to maintain some kind of balance
with the bacteria that are becoming increasingly resistant.
If we really want to end infectious diseases, we should go at least double or
triple the speed.
And we've been doing this this cycle.
During that time, as I say, 100 years.
And in this process, sometimes we have been a little ahead of
resistant bacteria, and other times a little behind.
Right now I'd say we're kind of tied, right?
But hey, here we are.
And throughout this process, we have developed many antibiotics, we have
stopped
using others that have lost effectiveness, and we are still here.
But in this process the bacteria have changed, they have evolved, they have,
they have, they have become resistant to many of the antibiotics.
I don't like this image because I think it sums it up very well.
In 1928, bacteria were sensitive to antibiotics.
We could throw anything on them and they would die.
And today we have super bacteria that are resistant even to the last line
antibiotics we use in the hospital.
So.
Well, this is it.
And as you know, this has had consequences.
Jessica has already mentioned it.
I like this fact because it exemplifies it very well.
It has been estimated that last year alone, antibiotic resistance or diseases
associated with antibiotic resistance caused 20,000 deaths in Spain.
That's a number only in Spain in a year.
It's a number.
It's a huge number, especially when compared to other numbers.
For example, this is five times more than the number of deaths in traffic
accidents.
And I would like to take advantage of the fact that these conferences are
titled about the silent pandemic to make a reflection.
I believe this pandemic is not silent in hospitals, it is a noisy pandemic.
In other words, we are very aware of what is happening.
It is a clinical problem that is seen every day in hospitals.
It is silent, perhaps for society, because its importance is not being
conveyed.
As I was saying, it causes more deaths than ours, traffic accidents, and we are
all
used to seeing ads raising awareness among drivers to wear their seatbelts.
Anyway, things that are very good.
I'm not saying that shouldn't be done, it's very important to do that, but
perhaps we should also do campaigns to raise awareness about this problem.
And well, this is one of the things.
And also, as Jessica has said, if we do nothing, the most alarmist
predictions from ten years ago say that antibiotic resistance
will cause more than 10 million deaths worldwide by 2050, not
being the leading cause of death in the world.
But here, in this prediction, which is a bit alarmist, there is a
part that I like: if we do nothing, I believe we can do things.
You who have participated in Micromundo and have done something, and we who are
in
the laboratory all day chipping away at the stone to try to find
new solutions, well, we are also doing something, aren't we?
So,
My view is that it is obviously necessary to develop new antibiotics, and that is
a very long and complex process, as you know, and one in which large
pharmaceutical
companies have to be involved, because it is very difficult to
do it from a small laboratory like the one I work in, right?
But what we can do is try to think outside the box
or try to find other types of solutions that aren't
so expensive to produce and that might help
fight this silent pandemic. Right?
So, as I was saying, we are now in this scenario where resistance is, let's
say, overcoming our ability to produce new antibiotics.
And I think what we should do, or what I can do, what I can contribute from
my lab, is to try to develop new strategies that we can use in combination
with these new antibiotics to overcome resistance. Right?
And I've depicted these strategies with this gentleman, like this, with virtual
reality
glasses, all very modern, because I think that's a bit of the future, what we have
to do from now until the future.
So, in today's talk I'm going to talk to you.
Well, many new strategies have been proposed to fight antimicrobial
resistance.
I had thought about telling you a little about all of them, kind of like a
class, but in the end I decided it's better to tell you about the ones we're
doing or researching in my lab, because well, they're the ones I know the
most about, which is important, and because, well, I think
they illustrate the ideas we have in the field quite well.
So today I'm going to talk to you specifically about two.
One is antibiotic repurposing, which involves using drugs that are
obsolete, that we no longer use because they have lost effectiveness,
and finding a way to make them effective again in some way;
it is a recycling of antibiotics that are no longer used.
And the second is perhaps the most futuristic, which is to use a
system called CRISPR Cas9, accompanied by Phage therapy to design
a kind of molecular scissors, an ultra-specific antibiotic that
allows us to eliminate only those bacteria that are resistant in a
population.
Well, it sounds a bit strange, but I'll explain it more calmly now.
So, let's look a little bit at the first one, this antibiotic repurposing.
As you know, the development of a new antibiotic is
a very long, very expensive process and full of possible failures.
First, we need to do a study, find a target, a site, a molecule,
something we can attack, a vulnerability of the bacteria.
Once we have found it, we need to look for a drug that is able to eliminate that
bacteria by exploiting that vulnerability.
Then some experiments are done in the laboratory, somewhat similar to those you
have done in
Micromundo, to see if that antibiotic is capable of killing bacteria afterwards.
That needs to be tested on a mouse, which is what it says here, "in vivo," right?
Then, once all that works, it goes to clinical trials and in
humans phase one is done to verify that the molecule is not toxic to humans.
Phase two is carried out, in which an attempt is made to demonstrate that it is
really capable of
eliminating infections, at least on a small scale, then phase three, and
finally it is registered.
This whole process can easily take 20 years from the time one finds a
potential antibiotic until one manages to bring it to market.
And in all these small phases there is the possibility that your antibiotic,
the one you are fighting to get and get, may not move on to the next phase because
it is toxic in humans, because it does not work as well as you expected in mice,
or for a thousand and one reasons, or because you are not able to produce it
in sufficient quantity to bring it to market, to get it to patients.
In short, it's a super complicated process and that's why, among
other things, it's so difficult for us to develop new antibiotics.
Well, this idea of ​​recycling or repositioning drugs tries
to skip all the initial phases and use drugs that are already
approved, that we already know are safe, that we already know work.
We aim to restore their effectiveness in combating antibiotic resistance, and
for this we rely on an evolutionary concept called collateral sensitivity.
This happens because of the bacteria.
This is a bit tricky, but I'll try to explain it well because I'm not very good
at it.
Well, it turns out that when bacteria acquire resistance to one antibiotic,
they sometimes become sensitive to a second antibiotic.
Okay. It's like a vulnerability.
They cannot become resistant to all antibiotics at once.
If you think about it, this happens in all of them.
In all living beings we have animals that run very fast and others that run a lot.
Or a person who is able to run a marathon, although that is not an
evolutionary example.
But okay, fine. Let's use the example.
I wouldn't normally win the 100-meter dash because you have to specialize, and
when
bacteria acquire resistance in some way they also specialize, and
when they specialize they lose resistance to other antibiotics.
And we'll see it with an example.
Imagine these two antibiotics.
Okay, we have this antibiotic that I represent here with a magnet.
This is an antibiotic that has fallen into disuse, that we can no longer use
because the bacteria
we find in the clinic, in hospitals, are already resistant to this antibiotic and
we have stopped using it.
But hey, antibiotics still exist.
We still have vials, we can still buy it, although it's practically not used
anymore, and then we have an antibiotic, B, which is super modern, although well,
I've drawn it with an arrow.
Maybe have a laser beam attached, but hey, you know what I mean?
The idea is not a modern antibiotic that we are using in the clinic and
that works very well, except when bacteria become resistant.
So, when we put the antibiotic on a bacterium like this, well, since this is
a
magnet and this bacterium has no metal in it, the bacterium is very happy.
It's durable and there are absolutely no problems.
This antibiotic is no good to us.
However, when we use antibiotic B, we are able to eliminate
this bacteria in the vast majority of cases.
But there is one case where this doesn't happen, and that is when this bacteria
becomes resistant.
And that happens because the bacteria, let's say, develops this shell that
allows it to
protect itself from this very modern antibiotic and this bacteria that is
resistant.
Well, right now she's so happy.
And this is a problem because we are already making it so that we can no
longer
use this antibiotic against these bacteria; it will no longer work.
So, what would happen if we used the antibiotic I showed you earlier?
The one who is a magnet?
Well, this bacterium, indeed, now has this metallic shell, let's
say in this example, and with the magnet and so it will work.
So now we have managed to make this bacterium hypersensitive to this
antibiotic, not to the antibiotic that was no longer in use.
Simply knowing how it will evolve makes it hypersensitive
to an antibiotic that we couldn't use before.
This is what we're doing in my lab.
We are taking very old antibiotics like Citro medicine, which is no longer used
except
for some very specific respiratory infections, and we are discovering that
bacteria
become resistant to last-spectrum antibiotics, as we are going to hear.
But it doesn't matter, cephalosporins become more sensitive to this
azithromycin.
It is an antibiotic that is no longer used, and so, by combining antibiotics,
we are able
to eliminate resistant bacteria that we would not otherwise be able to eliminate.
This requires a lot of work.
We need to investigate all the bacteria that are resistant, find out what other
antibiotics they have become
more sensitive to, and that's why it's not something that's being used in
clinics right now.
But I believe that if we continue working along these lines, we will be able to
develop these
antibiotic combinations using antibiotics that are already available to make
treatments more effective.
So, in short, what's this all about?
This is about finding that Achilles' heel, that vulnerability of resistant
bacteria, and developing combinations of antibiotics that are rationally
chosen, that exploit this vulnerability, this Achilles' heel.
And we can combine the two antibiotics or give sequential treatments, etc., etc.
And the other advantage of this type of idea is that it would prevent the
evolution of resistance.
When a bacterium becomes resistant to one antibiotic, the other kills it, and those
that do not become resistant are killed by the other antibiotic.
The first one, in short, is a game in which with two antibiotics you are able
to kill both the sensitive and the resistant ones.
It would be very quick to implement in the clinic because it simply involves
combining and changing
the treatments we are giving in hospitals, but there is no need to invent
anything new.
And well, this is an idea that I think is one of the
treatments that we could soon start seeing in the clinic.
Let's move on now, after the recycling of antibiotics, to this
other idea that we are developing in my laboratory,
which is the use of CRISPR Nine and Phage therapy.
I'm going to tell you a little bit about all this.
This responds to a clinical need that exists in the hospital, in
hospitals, when a patient is admitted for any reason, because
they have broken a leg, because they have any type of disease not
directly related to antibiotic resistance, what often happens
to patients, especially when they are older, is that in their
digestive tract, as you know, they harbor a microbiota, a lot
of bacteria that are there naturally, as we all have.
But patients who are hospitalized for a long time end up being colonized by
resistant bacteria.
Another one from Mexico here, these little red ones that I'm showing you
here.
Okay?
This happens because the resistant bacteria is very skillful and is able
to live, colonize, and establish itself in people's intestines from there.
It's not symptomatic, nothing's wrong, you have it in your intestine but you
don't notice anything.
Let's not say it doesn't cause any disease.
But what is known is that patients who are colonized by these bacteria have a
higher risk of developing infections.
When bacteria move from the intestine to other areas of the
body and are also able to transmit to other patients within
the same service or the same hospital ward, it eventually ends up.
We end up having entire wards or entire departments of the hospital
with patients with high rates of colonization, and that indirectly causes
infection rates to rise.
In short, it's a serious health problem, let's say, and we don't have an easy
solution because we can't give antibiotics to these patients because
they
don't actually have any infection, and using them would be like using a
sledgehammer to crack a nut and we would be digging our own grave
because we would be facilitating the emergence of resistance.
So, in my laboratory, what we have invented is this concept of autobiotics
that I am now going to explain to you.
What we do is a good thing, a little scatological, and
that is that we can take fecal samples from, well, here
we can take fecal samples from patients.
These fecal samples, the poop, contain the patient's microbiota,
all the bacteria that populate that patient's intestine.
Then we developed a method that allows us to isolate this microbiota, separate it
from
the fecal matter, eliminate the feces and keep only the bacteria, which is
ultimately what interests us.
And once we have this isolated microbiota, we are able to treat it with
this
ultra-specific antibiotic that I am now going to explain to you and eliminate
only
the bacteria that bothers us, which is the red one, the one that is resistant.
And that gives us a healthy microbiota that we can reimplant in the
patient, put into some little pills and give to the patient to take.
In this way it would work as a kind of probiotic, not like the Actimel you drink
in the
mornings, but much better because this month instead of just having a
lactobacillus,
it has the entire microbiota of the patient, all the part of the microbiota
that is
healthy, that is correct, that is diverse and necessary for the functioning of the
intestine.
And we have selectively eliminated the harmful bacteria.
So this sounds really cool, but here's the hard part.
How do we do this?
How do we eliminate just one bacterium within a complex and very, very diverse
population?
Well, we use the CRISPR Cas9 system.
I don't know if you're aware of it, but this has been a revolution in modern
molecular biology.
It was discovered by a man named Francis Mojica in the salt flats of Santa
Pola in the 1990s, and after his work many people have appeared and
finally Jennifer Luna and Emmanuel Charpentier were given the Nobel
Prize for the use of this technology to edit genomes.
And this will allow us to cure a lot of diseases and it's really a revolution.
And what's important for you to understand is that what this allows us to
do is
examine the DNA of a bacterium, which is that string of letters that
encodes all the information that the bacterium needs to survive.
Antibiotic resistance will also be coded.
So with this technology we can look for that specific sequence
that only codes for antibiotic resistance and will
only have those bacteria that are resistant.
And that will cause this system to produce a specific
cut in the DNA of that bacterium, and DNA cuts are lethal.
Only those bacteria that have the sequence we
want, in this case a resistance gene, will die.
The problem with this technology is that it is very difficult to make it reach the
bacteria.
In other words, this works very well in a test tube.
This works amazingly well.
But how do we introduce this technology into bacteria?
Well, the real problem is, well, if you imagine that's a bacterium, okay?
And this is the DNA of the bacteria.
The real problem is that the membrane, the envelope of the bacteria, is actually
not very permeable.
The bacteria have decided, they decide what goes in,
what goes out, and they do it in a very specific way.
And it's really very difficult to introduce things through that membrane,
through that bacterial envelope.
Okay, because it has many layers and is very permeable.
So what we did in the lab was, well, design a Trojan
horse that allows us to trick the bacteria
into introducing the CRISPR system.
And that Trojan horse is a bacteriophage virus.
Here's a little drawing.
But bacteriophages look like this.
And these viruses are naturally occurring viruses of bacteria.
Just like we have cold or flu viruses.
Bacteria have their own viruses that cause colds or worse,
and we can take those viruses in the laboratory, modify them,
use them at will, unify them at will so that instead of putting
in their own genetic information, they put in our CRISPR, CAS system.
And these viruses are very good at putting things inside bacteria because
that's how they live, by infecting bacteria.
So with this system, can we now use our method to kill sensitive bacteria as we
do now?
Well, we have these bacteriophage viruses that are going to attach to the bacteria,
they're going to work like a Trojan horse, they're going to introduce this
CRISPR-Cas
system that's going to recognize the resistance gene that you have there, in
that
little red square, only and exclusively that resistance gene.
The system works like scissors cutting DNA.
That is lethal to the bacteria and it dies.
This sounds a bit like science fiction, but it works.
When we put the bacteriophages we make in the lab into
fecal samples from patients, this is what we see.
Well, I don't want to bore you with the data, but basically we
are able to eliminate more than 99.99% of the target bacteria without modifying any
others.
In other words, the rest of the bacteria in the patient's healthy microbiota are
still there.
They're healthy, they're alive and kicking.
We only killed the one we wanted to kill.
So this is a hyper-specific system that is very advantageous compared to other
systems like antibiotics, which are somewhat non-specific.
That's one part of the problem.
We not only kill the bacteria we want, but all the others as well.
So with this we have developed these autobiographical systems,
which are very versatile and allow us to modify the human microbiome on demand.
And this has implications that go beyond antibiotic resistance.
Because, well, it is known that the microbiome is the collection of bacteria
that lives in our gut.
They affect many other diseases such as neurological diseases and such.
And this, well, could work in that sense.
The only problem we have is that we probably need to change the legislation
to
make this possible, because right now there is no legislation that allows us to
use this on humans.
There is still a lot of work to do; we have to conduct clinical trials.
Anyway. Well, but that's one of the problems we're
going to look at, and well, that's what we do.
And what can you do?
I was wondering, it seemed to me that it would be relevant to talk about what you
can
do, since many of you have participated in Micromundo, which is already quite
something.
But anyway, I brought this pamphlet from the World Health Organization,
which basically tells you that all you have to do is use antibiotics
properly, as and for as long as the health personnel say, and wash your
hands; these are the recommendations of the World Health Organization.
I think it's really important that we use antibiotics properly, but I also think
there are other options.
Well, apart from that, there's something we all have to do.
You also have the option of becoming scientists and doing your bit to try and
solve this.
This problem.
I don't know how much time I have.
Bad, bad, bad.
No? Well,
Well, this is a picture of the lab.
So here I have a place where I can stop or show you something to motivate new
generations to become scientists.
I think I'm going to teach it.
Okay, this is an illustration that I really like because I think it
exemplifies a lot of what I feel, which is science, what
science means to me, and working in science every day.
Imagine that this circle you see here is all human knowledge, everything is
in there, it's there, Mozart's music is there, Fleming's penicillin is
there, your grandmother's paella is there, everything that humanity knows is
there, okay?
And when we are born and grow up, we acquire knowledge.
That, that little part.
We don't know how to walk, crawl, or cry when things go wrong.
Then we'll talk about forgiveness.
We go to school and learn a little more.
That's where elementary math comes in.
Well, anyway, a little bit of literature, things.
Then we go to high school and university and we start
learning about everything that life is about.
But this structure, which is a more specific knowledge, begins to appear.
If you go to university and study biology, or in my case, for example,
which
is what I did, that's biology, knowledge that one acquires from biology.
Then maybe you'll do a university master's degree in something even more
specific.
Sorry, I'm having a terrible time with this pointer on a more
specific thing, which is what molecular biology research is,
and you gradually specialize more and more and then if you want
you do a doctorate, which is four years in the lab trying,
investigating some problem and you get to a very specific place,
which is there. Okay, that place is one of the most wonderful
places in the world because it is the frontier of human knowledge.
There you are, here, and beyond that, nothing is known.
It is, it is, it is, it is absolute ignorance.
And then what you do is work really hard and do a lot
of experiments to achieve something like that.
A small push at the frontiers of human knowledge.
And that could be a small discovery against autobiotic
resistance, or it could be anything else.
And that's fascinating, because in reality, for you, this is what it looks
like during those
four years that you're struggling with that insurmountable wall of human
knowledge.
It is a very hard and difficult thing, full of failures and frustrations.
But at some point you achieve it, and however small that effort may be, you
have
contributed to human knowledge in a practically significant way.
A tiny thing, practically ridiculous if you
will, but humanity now knows more than before.
Thanks to your work and the work of many others, we are able to advance human
knowledge.
So, well, I think that's one of the best things you can do in life, and that's to
work
on trying to advance human knowledge rather than getting into
the same place as Newton, Einstein, and your grandmother.
So it's a spectacular place and nothing more.
That's all. Thank you very much.
I wanted to ask if there will really be future
applications of the therapy and what you have done.
Autobiotics, probiotics.
So, is it really viable?
Because from what I understand, when a person is in a hospital
and has a serious infection, sepsis or something like that, even
if they do tests in the labs for antibiotics and all that, it takes quite
a long time.
For example, a new culture can take up to five days to test positive.
So, if applying that can actually speed up the process of
applying a treatment, because of course, until a positive
result is given, I understand that more generic antibiotics
are given, to which there can also be resistance.
You're absolutely right. What we're doing in hospitals right
now is giving empirical treatment. We know roughly the
prevalence of resistance, so we choose a treatment that, if
everything is statistically normal, is expected to work. Right?
But this idea doesn't go in that direction.
No, we don't want to treat acute infections, like sepsis, not things that
could kill you by tomorrow.
We just need to use the antibiotics we have available, that's all.
I don't intend to replace that because... Because it would be very difficult.
This is somewhat aimed at treating other patients who are not in such a hurry,
those I was
telling you about who are colonized, who are fine, nothing is wrong with them,
it's just
that it is known that they have a greater risk of developing an
infection, of getting an infection and of spreading the resistance.
So the idea would be to fight it before that infection occurs.
It's a bit like a preventative measure, you know? Right?
They simply have to take a capsule of their own treated microbiota and
that should displace the resistant bacteria from the gut.
Okay, two related questions.
Okay, you can understand one and then not the other, because they all follow one
another.
And as for the sequential ones, they are trying to do it separately, but
no, because I understand that the objective is for you to know which clones
are spreading in the community and you say, well, I'm going to design a
phage against these clones that carry this very bad enzyme that eats this
antibiotic, because the idea would be to make it preventive.
As I just explained.
But what's going on? Or have you tried it?
What happens when that microbiome is also exposed
to antibiotics, at concentrations that could
select for resistance to the Phage itself?
That's been studied. Are you looking into it?
No, of course not.
This is one of the problems with gene therapy in general and this approach in
particular.
Bacteria develop resistance to antibiotics and phages, and also to
anything
that might kill them, because they change and adapt just like all living things.
So the answer is to try to use it.
That is, the idea behind this.
Right now we are still in a very, very early stage of this project, but
the idea is to develop a cocktail, to have a cocktail of phages that
target different antibiotic resistance genes that we know will be
prevalent in the laboratory and that should mitigate resistance.
If you have different phages that are going to enter the bacteria through
different routes, that should make it easier.
But well, these are things that definitely need to be looked into.
Hey, one thing for those of you who have added the code for the credits
new vouchers.
Okay.
We now have the honor of introducing Belén Aracil García, senior scientist
at the National Center for Microbiology of the Institute of Health.
Carlos Tercero is a recognized expert in antibiotic resistance,
with extensive research experience focused on the surveillance
and characterization of resistant bacteria.
Belén has participated in national and international monitoring networks,
contributing to the establishment of control strategies to address this global
problem.
His publications and scientific collaborations have been key to
improving knowledge about the spread of resistance.
In his talk on Antibiotic Resistance, he will help
us to better understand this challenge.
Thank you very much for the presentation.
Thank you so much for inviting me.
It's a pleasure.
It's a bit difficult for me because it's a very diverse forum, because
we have everyone from institute staff, undergraduate and postgraduate
students, professors, uh, so well, I'm going to try, uh, to make it
suitable for all of you so that at least some part of it contributes something to
all of you.
And well, anything you want to ask me or that wasn't clear, well,
here or through my email or whenever you want, okay?
And well, uh, kind of what they've said.
I'm a doctor from the Autonomous University, you know?
I specialized in Clinical Microbiology and Parasitology and
joined the Carlos III Health Institute, at the National Center
for Microbiology, and I have been working on antibiotic
resistance for 30 years. This center, which has now been
modernized, and as you can see in these very innovative
facilities, has a kind of quadruple focus. Firstly, we are
dedicated to the reference diagnosis of everything that
hospitals do not diagnose and want to go a little further or do not have the means
to do so.
When we take charge, it is a monitoring program of what we have, which
is voluntary and free and which provides service to all Spanish communities.
Then we have a surveillance operation; we monitor the most prevalent clones
and epidemics and everything that is supposedly circulating in the country.
We characterize it by different means, different
methods and lately mainly by massive genome
sequencing. We have a research part that, as you
can see here in Pichar, has about 20% in which we
carry out different lines of research,
especially thermal resistance.
The last line is already controversial.
Step.
And well, then we have teaching, we have teaching for the 4th year of
ESO plus business program, we have teaching for laboratory
technicians, we have undergraduate and postgraduate university
courses. So we cover a very wide range of different scenarios.
Well, to bring microbiology a little closer to everything, to all teaching.
And well, what can I tell you?
So I'm going to give a general introduction, I'm going to talk to you
about bacteria,
mainly for the section for people in secondary school, eh?
I'm going to talk to you about resistance, antibiotics, and then I want
to give
you some general conclusions that I think will be useful to all of us.
Well, no, I don't know, I don't know.
I have shown this emblem that is also on the poster, which is an emblem
that is now like the one that tries to popularize what is the commitment to
resistance.
Antibiotics is an emblem of a Swedish boy who entered
it in a contest and won, which is a bit like that, uh,
commitment, no, love is a band-aid too.
And at the same time, they are two capsules of antibiotic that he is trying
to take.
Well, a little bit, uh, to give it this three-pronged approach it can have,
right?
The resistance treatment?
Well, they are bacteria.
Bacteria are the most primitive living beings, they are 4 1,000,000,000
years old and are also the most abundant on the planet.
As you know, they are adapted to any condition and any habitat.
And well, they belong to the prokaryotic superkingdom and have two domains: the
archaea domain, which are not pathogenic in principle, and the bacteria domain,
which are pathogenic, and they reproduce every 20 minutes.
So this gives us a possibility of change and variation that
we could not have except in millions of years,
well, thousands of years in mammals.
So of course, this allows them to have that versatility and variation
that makes them adapt to any medium, as has already been said in this forum.
And well, they can colonize and they can infect all those with whom they colonize.
They are not malignant; some are part of our microbiota and we even have
to preserve them because they protect us from, or prevent us from being
colonized and confronted by, others that are indeed more numerous.
You all know him, right?
We have an active natural immunity versus the passive immunity that
is transmitted to us by our mothers during pregnancy and through
breastfeeding.
Sometimes it's nonspecific, natural, killer
phagocytosis, complement, interferon, eh?
And then there is another one that is specified as normally mediated
by T and B lymphocytes, which you then know create memory.
And well, you know that we also have information that can be passive.
For example, these.
Do you remember Ebola when there was no way to treat it, and then a person
was brought in, or permission was requested from a person who had
managed to overcome the infection and those antibodies.
That person who had already created immunity was given to another person
after
passive immunity and then active immunization from vaccines.
You know that there are many types that unfortunately.
Well, it's the vaccination schedule of the Community of Madrid, but it's not the
same everywhere.
And what do I say is unfortunately, because I think there are very good
things
about the transfer to communities, but this was a bit controversial because
it depends on where you are and how you are, whether you're vaccinated,
some things are covered, others aren't, right?
Some are funded and others are not, but well, this is our current one from the
Community of Madrid.
And then the other answer is the curative one, the phages, which
Jerónimo has already mentioned a bit, and well, antibiotics are
a bit more my field of expertise, in which I think I am a bit more
knowledgeable, which are antibiotics, well, antibiotics are
medicines that fight bacteria or prevent their growth.
So the concept of it being bacteriostatic or using its death,
which is called bactericidal, was where they act at different levels.
This is a bacterium in a schematic way, since they can act at the
level of cell wall synthesis, at the level of nucleic acid synthesis,
at the level of protein synthesis, and so on, at the level at which they act.
Well, we have the opportunity to fight it in different places.
They are different mechanisms. What's happening?
The problem we have is that antibiotics are being created by the
bacteria, due to its versatile ability to create resistance and
especially because of the frequent divisions every 20 minutes.
Well, it's able to avoid these antibiotics.
What I'm telling you.
Ability to develop different mechanisms to survive antibiotics
and great ease in exchanging information through transfer plasmids.
So it makes the original bacteria, well, maybe in less than a day,
especially if it's subjected to antibiotics, right?
Well, it makes one that thanks.
This is a slide that shows it to us, huh?
Visually very good, because here we have a different population
in which sometimes only one is resistant.
The thing is, with antibiotic exposure, that
exposure only selects those that have
something to A in different directions.
What it does is select only the one that has the change or only the one that
avoids the medication.
Avoid sensitivity.
This, well, we have already mentioned several times throughout the morning.
Is that Alexander Fleming, huh?
Penicillin was one of the major milestones in history.
I imagine it's a story that was completely accidental.
Not by leaving, uh, Al on a long weekend, a bacterium
exposed, uh, to the environmental conditions, was
colonized by a fungus that is what he saw.
As you can see here, she has a sensitivity that could have some power
against them.
Huh? What did he achieve?
Well, look, this is what we had before around 1942, which is considered
the end of the antibiotic era, which is when antibiotics began to be used.
This is a case of a septic cell, uh, with a staphylococcus aureus.
A girl who got a sharp object stuck here in her jaw.
Well, this is what we had before.
We had cellulite.
Uh. Well, uh, it was terrible in, uh, in what is the,
sorry, in what is the mandibular area, even
hereditary, and this is what was achieved with
the antibiotic treatment 15 days after the...
So, what did this mean, or did it mean a change? Huh?
Absolutely. Uh, uh.
How do you
eh?
Well, it was unprecedented, wasn't it? At first, there was a bit of
triumphalism because people thought we had eradicated infectious
diseases, that we were completely immune to them, and
that from now on there would be a before and after.
It is true that there was a before and after, because the evolution
has been completely different and then they began to create different
drugs and molecules that were derived from or had the same
intentions or the same mechanisms as the first ones.
But unfortunately, despite that situation, there
has never been a better situation than this one.
Do you see, if you look at the causes of death from
infections in the 1920s, how these deaths decreased over time?
Well, these are all the causes.
For the causes.
These are the causes that are not things that have followed the same temporal
evolution.
These are the causes that were infectious and that, with the
chaotic administration of therapy, were decreasing.
But this, uh, at the beginning, uh, was a triumphalist perception that was had.
Uh, if you look at the timeline, the timeline above tries to
show the synthesis of the different substances or the
different families of antibiotics with the different mechanisms over time.
The 1930s to the 2000s.
This timeline below is the emergence or development of the resistance.
But if you look closely, it happens practically from the
moment a molecule starts to be created, right?
Well, a few years later, sometimes a few months later, resistance
mechanisms to those same molecules begin to develop.
That's why Jessica mentioned at the beginning of the talk
that Fleming was very visionary and said from the beginning
that if people weren't capable, of course, if they behaved
ignorantly and weren't able to use these molecules correctly,
then their days were numbered, because practically, as you can see.
From the moment of their creation, resistance
began to appear, right? And what has happened 80 years later?
Well, you've probably seen popular science magazines that talk about super
bacteria.
It's a term that microbiologists don't particularly like, because
they're not super bacteria, but it's true that antibiotic pressure and
evolution have allowed us, thanks to the versatility I mentioned in
bacteria, to now have microorganisms that are not very difficult to treat.
So these are all the bacteria we know of, huh?
In our environment, these are only the ones that are pathogenic in humans. These
are the ones that are resistant to some antibiotic, the ones that
are multi-resistant, the ones that are extremely resistant.
They only have two families of antibiotics left, those are the ones they
don't have left.
And that's because it's a small subset.
But of course, what's the problem?
That this small subset is grouped in a space that is of
people who are susceptible, is of people who are
vulnerable, have immune defects, are treated.
So this is really difficult, huh?
After arriving at solutions, we need to make sure
they are successful, because, as I was saying,
medicine isn't like it used to be. Medicine used
to be more limited, but what do we do now?
We perform organ transplants, we have chemotherapy for cancer,
we have intensive care units, premature babies are increasingly
premature and almost all have a very high survival rate, which is
an achievement for society and for our current medicine.
But all this means that therapy is essential.
So, of course, this severely limits the options.
When we find ourselves in that small
rectangle or square that I showed you.
What can also happen is that all of this is usually centered in hospitals
and therefore has a very large impact on nosocomial outbreaks.
Outbreaks are when in the same place you know that for
there to be an outbreak, it has to be, uh uh, that the
bacteria are being produced equally in space and time.
So if they all accumulate in a place that is an intensive care
unit, in a place where there are people who are very vulnerable,
then we have bacteria that are very resistant at the patient
level, so the therapeutic alternatives decrease, and they
suffer increases in morbidity and mortality, right?
We need to try other alternatives and synergy with antibiotics, but this also
has a
community-level dimension, because there is a risk of dissemination in the
hospital,
between hospitals, and we need to assess these risks and take control measures
because there could even be cross-border outbreaks.
We now live in a global society where there is more and more
travel, and we are all increasingly in contact with each other.
So the possibility that this could escape borders and go to
other places is also a very worrying threat.
And there is a paradox.
The paradox is that at the same time as resistance is increasing, the development
of antibiotics is decreasing.
That's why we need to be more creative and create new alternatives.
And why do you think this is?
Well, the truth is that it's not profitable.
So, how would you say it's profitable? Why is it profitable?
Because it rents because it is a self-limiting infection in terms of time
and people.
And then you spend 20 years developing research
to put it into a very limited treatment.
If you develop an antelope using oral diabetics, well, that's it.
Doesn't this produce an economic increase for commercial and pharmaceutical
companies, which is ultimately how they finance themselves?
Which is much more than creating an antibiotic.
So, I think that's partly why we've had a bottleneck.
And well, a bottleneck, because in recent years only antibiotics
derived from already known families had been created, and currently
new antibiotics are related to the synthesis of inhibitors, which
are like combinations of the previous ones, or as Jerónimo has also
told us, resorting to antibiotics that were somewhat obsolete and that have now
been used again.
I think we've already mentioned this several times during the talk.
The burden of multidrug-resistant bacteria creates an
attributable mortality of 25,000 people per year and an
additional 2.5 million hospitalizations per year.
Hospital costs €900.
Productivity losses, 600 million.
This, which seems to be about money, is of great interest to hospital managers.
Well, you can tell him that there's something very important you want to buy,
but he won't finance it.
But if you speak to him in economic terms, that is, if you
tell him that it is avoidable, not only because of the disease
it causes, but also because of the monetary savings it
causes, then that is also an advantage we can use, because
this is true and it is also true that this gentleman, the
British economist, who has been mentioned twice already,
was hired by the government of Cameroon to do a report that
was of the highest level, the one that quantifies the
impact of antibiotic-resistant bacteria.
So this is basically a summary that's already been discussed twice, right?
He commented that 100 million deaths could be attributed
to the year 2050 if nothing was done.
While it is true that we have in our hands, well, the advantage of being
able to be, uh, uh, aware of the situation above all and be able to take
measures in this regard.
The $20 million figure each year also seems like a significant
amount to me, and well, it's just one, you know?
That one, eh
Its importance, of course, lies in terms of human
losses and loss of life, loss of health and morbidity,
but economically it also represents a
significant expense for everyone.
I'm also using one of the many
infographics that the WHO has
to raise awareness. I've put it
here so you can see how we're all involved.
In the selection of resistance propagation.
Antibiotics, huh?
The person who goes to a hospital, uh, causes a selection of those
bacteria and they spread, and then that spread can occur to the general
population.
And also because you know that it has been poorly regulated over time, right?
The addition that was made so much in antibiotics, uh,
to food as well as on farms, because you know it's a growth factor for animals,
uh?
If you have an agent, that is, some animals that are tabulated and
that are in an intensive production and they are given antibiotics,
since they are all in contact and infections are
prevented, especially when it is beekeeping, eh?
More so than the coil.
Well, what happens is that, uh, you get higher meat
production and higher economic income.
So for a very long time, both animals on
farms and their food have been indiscriminately
supplemented with these antibiotics
because better profits were obtained.
Was it paid for afterwards?
So, what are the consequences?
Well, because right now there are so many, uh, children, for example babies,
that you
do a blood test and they have markers of resistance without ever having consumed
antibiotics.
And that's because all the foods that have consumed milk, including
infant formula, have been derived from products that have been supplemented with
antibiotics.
And so right now if we take different samples at different
levels, uh, ecological, environmental and food, we can find food remains.
Fortunately, there have been some plans, especially in veterinary
medicine, like the plan, for example, for choline control, which
they will surely tell you about at the last minute, which has greatly
reduced that consumption and has controlled this situation, but
which until a few years ago was very worrying.
And well, it has importance from an ecological perspective, because it
is a public health problem recognized as a priority by all
agencies such as the WHO, the European Union or the CDC.
And from an individual perspective, of course it is a clinical and therapeutic
problem, since it conditions the evolution of infectious diseases.
It's a bit like what was shown in the previous slide, or Angels, but
this is very trendy right now, and what it's trying to say is that
the entire environment, animals, people, and the consumption
of any product currently need to be regulated because we are all
co-responsible for preserving these antibiotics that will be useful to us in
the future.
Well, this is kind of the same thing.
Um, I want to emphasize that it's important that we control the use
of antibiotics, that they are used prudently, because the
use of antibiotics is what selects in a certain way.
The resistance of the commensal flora causes the resistant
strain to spread, which the patient with an underlying pathology
may be vulnerable to and then may manifest an opportunistic infection.
So antibiotics are really the only molecule, the only drug whose
adverse effects not only affect the person, but can affect other different
people.
And I also want to send you this message that I hope will stick, okay?
Okay, antibiotics are used to treat bacteria.
Most of the common respiratory illnesses that
occur throughout the winter are caused by viruses.
An antibiotic will never be effective against a
virus, so maybe we have to do quite a lot, huh?
It's also about teaching, but not only to this forum, to the general
public, that antibiotics should only be used when they are truly
going to be useful, because they are useless for colds.
So, well, I'm going to put this here many times simply so that
this message, those things are not useful for
treating colds, because they are not used.
Okay?
Well, I also want you to remember that the inappropriate use of antibiotics is
the main cause of resistance.
So, if we use antibiotics, huh?
Did Jerónimo also tell us that they should only be used
for the time and with the instructions that the doctor tells you?
It's true that in this country the antibiotic box is poorly designed
because there's always too much or too little. So you always have a
remnant in your bathroom cabinet to use later, and you shouldn't throw it away.
You know that in pharmacies it is only disposed of at the time and with
the prescription and with the indication that the doctor or the person treating us
has told us.
And that's it, some conclusions that antibiotic resistance and
multi-resistance
are constantly evolving and have important implications both clinically
and for treatment.
Uh, it's true that it's a random event, but it generally prevails
among the universe of bacteria in the use of antibiotics.
Select this resistant strain, making it predominant, and once the
mechanism is selected, it can spread and perpetuate itself.
The responsible use of antibiotics is key to reducing this first step,
and continuous surveillance and the study of resistance mechanisms
via dissemination are essential elements in this control.
And I want to send you three messages, the one from Walsch, which I've already
told you about.
So we are all responsible in every area: food,
veterinary medicine, the environment, etc. Prudent
use is very important, as I've said, and as has also
been mentioned here, hand hygiene is very important,
both for us and for healthcare personnel, because
it prevents a very high percentage of cases.
In fact, we just celebrated May 5th,
which is Handwashing Saturday.
Just as there is a use, there is a day for the prudent use of antibiotics, which
is November 18, and with these initiatives we try to popularize and
spread awareness.
These initiatives are fundamental and key, because they will
allow us to use the antibiotics we don't have tomorrow.
These are all the organizations with which we collaborate or work.
This is my research group, the Carlos III of FNM, and well,
I'm leaving you with this message that we are all responsible
for ensuring that we don't find ourselves in this situation
again, in this beautiful golden picture where we return
once more to the era of major infections and the pre-antibiotic era.
And thank you very much for your attendance.
Thank you so much.
Infections caused by bacteria, not viruses.
The problem is that many of these microbes produce,
let's say, pathologies with the same symptoms,
such as fever, headache, sore throat.
But having a fever does not mean that we have a bacterial
infection and that we need to use an antibiotic.
Okay, it's very important that we understand this clearly.
How do these drugs work?
Well, because of the principle of selective toxicity.
What does this mean?
They will act in specific, important, vital places
for the bacterial cell, but they will not act on our
cells, nor on the cell of a virus, nor on the cell of a
parasite, because they have nothing to do with each other.
Okay, normally, because they act in vital sites
such as the cell wall, the cell membrane.
They inhibit protein synthesis, the synthesis of genetic
material, or function in metabolic cascades that synthesize
vital substances for the bacterial cell, such as folic acid.
Okay.
Okay, that's one thing, huh?
Antibiotics, as we have already discussed, were centered
or emerged with the discovery of penicillin.
I really like the discovery of penicillin because it is a
clear example of what it means to work as a team.
One person alone won't get very far, but if they work in a
research team, they can go very far and achieve great things.
And that's what happened with penicillin.
Dr. Alexander Fleming was working with cultures, in this case of Staphylococcus.
Okay, as we can see in the image, he went on vacation and when he
came back, he saw that there was something strange in his Petri dish.
This thing here, which was a bit environmental, the plate
was contaminated with penicillin, not Tatum.
And he saw that the bacteria he had cultivated there did
not grow around that fungus and he thought, "Ah, well then
this fungus has released something." He called that
something penicillin, and he saw that
penicillin inhibited the growth of those bacteria.
And that's where it remained, as an anecdote, a laboratory experiment, after
all.
And it wasn't until later with these very serious gentlemen.
Flores in the year 39 who returned to this discovery
and were able to purify and produce this penicillin
on a large scale in order to, what they wanted was
to demonstrate that this really inhibited an infection.
So what they did was take a small group of mice, inject them with
a deadly bacterium, streptococcus, then inject them with
penicillin, and they saw that only those mice that had penicillin survived.
They had already demonstrated that penicillin
could inhibit or reduce an infection and keep those infected mice alive.
Okay, this was a great discovery that was later...
These three researchers were awarded the Nobel
Prize in Physiology or Medicine, and later, in
1941, clinical trials were conducted with people
to study the effectiveness of this antibiotic.
But the big boom was its use in World War II, where
practically every soldier carried a backpack
with a dose of penicillin to combat those
war wounds and many lives were saved.
Okay, a lot of lives.
That was, therefore, a revolution in medicine, and
later penicillin began to be used in the civilian population.
During this revolution.
Of course, many more antibiotics came along.
Everyone wanted to design new penicillins,
new antibiotics, and here we can see on a timeline
from the 1900s to practically 2025
how things have gone last year.
Is this a very, very, very brief summary?
So how has the industry
developed in these times?
We can see that the great golden age of antimicrobials
was from the 1930s to the 1950s and 1960s.
We see all this yellow part of yellow arrows.
These are drugs, antibiotics that have been developed and
we have many gaps, many empty spaces where there is no
drug design, no new drugs, as is happening now.
Lately we have seen that, uh, the problem
with the lack of these new drugs is due to the
red line, which is the emergence of resistance.
Okay, if we look at penicillin and it was put on the market
in 1941-42, we can see that there were already resistances.
Five years later, five years later there was already resistance,
and Mr. Fleming had already predicted this.
If we go to the last drug that appears on the list,
except for Sano Vale which was marketed in 2004,
we see that it already has resistance in 2021.
Seven years later, there are already bacteria resistant to one of
the new antibiotics that has been developed recently.
Okay, so as my colleague Belén said earlier, this isn't profitable
for the pharmaceutical industry. Nobody wants to lose money
or invest a lot of money to bring a new drug to market, knowing
that in five years it won't have the same effect.
than before.
If we think about what these antibiotics have given us, what has been the clinical
impact?
So think about all these images I'm showing you here to heal a wound.
Imagine if they said that in ten or twenty
years, a small wound on your skin could be fatal.
Okay, because I could do it.
In fact, there are already people dying from poorly healed wounds
because there are no antibiotics in that person that are effective
in curing a possible septicemia that may develop after that wound.
Okay.
Well, the uses I've given you are very illustrative, aren't they?
A bacterial infection in the hospital can be treated, but it can also be prevented.
Patients are often given an antibiotic to prevent future infections, such as...
When we go to the dentist, someone who hasn't been to the dentist has had a
tooth pulled and
they've been told, "Well, now you have to take an antibiotic for a week."
It's to prevent infections.
After they perform that extraction in the operating
rooms, they make an incision, right?
Well, that incision will be in contact with bacteria that
may be present in the operating room environment, on
surgical equipment, or on the gowns of the professionals.
No, although everything is in a sterile environment, we are never free
from the possibility of some bacteria being out there causing some
harm to cancer patients, to transplant patients who are going to undergo a
transplant.
Many of these chemotherapy treatments produce immunosuppression.
The immune system becomes weaker, and these patients
may be more susceptible to developing an infection.
An infection is valid, as are transplant recipients.
So, look at all these examples.
Well, great discoveries or great advances in modern medicine.
If they couldn't be carried out, well, we'd die very
easily, right? And if we think about it from a
pharmacological point of view, why
would we want to use antibiotic treatment?
We need to be clear about two very important things.
Okay?
And this is already related to the rational use of antibiotics,
the good rational use of antibiotics.
Well, to treat an infection, the antibiotic has to reach an
optimal concentration, usually higher than the minimum
inhibitory concentration, which is the minimum concentration
we need to stop the growth of bacteria at the site of infection.
So we need to think about where we have that infection?
Where is that focus?
In urine, in the lungs, in the brain, in bones, in blood.
It's not the same as treating a urinary tract infection where
we might take some sachets of medicine orally and have the solution in a matter
of a day.
The infection is very well controlled.
Okay, the drug goes to the kidneys, is eliminated through
urine, and that's where it will have its effect. Okay.
That bactericidal effect is very easy to achieve.
Okay, in theory there are no resistances.
On the other hand, an infection that is in a bone is more complicated.
These treatments are much longer-lasting, with higher
concentrations of antibiotics, because a bone is quite
hidden and the drug has to travel a long way to reach that
bone, to that focus of infection in that bone.
Okay. Good.
Therefore, the effectiveness of antibiotic
treatment will always depend on the concentration
of the antibiotic and the treatment time.
Okay. And the doctor knows this.
The doctor knows how much to dose and for how long, because
that is already evidenced by the clinical guidelines.
Okay, we don't know.
That's why we have to listen to what the doctor tells us, that a treatment
lasts seven days, because we shouldn't interrupt it after three just because we
feel better.
Do we have to last those seven days
and take it as specified, okay?
The goal is not to kill bacteria with a cannon.
I'll take an antibiotic now and that'll be it.
There's no need to overthink it; we need to expose
those bacteria to the correct dose and for the correct
amount of time. Otherwise, we'll create an environment
rich in antibiotics at doses that are therapeutic,
doses that are not effective at a therapeutic level.
In that poor environment, what we'll do is allow the
bacteria to have free rein to transmit genetic
material, to mutate, to transfer plasmids, and
ultimately to become resistant.
Okay, and we can't afford that kind of environment.
We cannot achieve that, we cannot give bacteria that break.
Okay, then the only way is to do it with the
correct doses and the correct time.
Uh, sometimes the treatments.
Well, the doctor doesn't have to know them beforehand, not in very serious or
unknown infections.
Do we need to resort to further antibiotic
testing to see what that bacteria is sensitive to or resistant to?
In this box, I've included a urine sample
that has been cultured. Right?
Have different antibiotics been tested on the mirabilis
bacteria, and does this show what that
bacteria is sensitive or resistant to?
Okay, in this case.
Well, we have that it's sensitive to it. Isn't that right?
No, if that's the case, then no.
That would be the correct antibiotic.
Okay, but as I was saying, this has to be decided by the doctor.
We cannot self-diagnose or self-medicate.
Okay?
Is it the doctor who has to give us all this information,
right? Regarding antibiotics, which are essential medicines
for humanity because they save lives, right?
The WHO has listed 41 of them, out of all the
hundreds of antibiotics that exist, as essential antibiotics.
Okay.
And those essential antibiotics are in turn classified using a traffic light
system.
Green light, yellow light, red light to optimize its use.
OK.
So we have that, it's called the aware system.
Vale from English a of access or a of watch of
surveillance and reserve network or reserve.
Okay.
Therefore, doctors have to optimize the use of
these drugs, so that the antibiotic drugs that
should be used most are those in the green category.
Okay, because they are very safe drugs, with few adverse effects.
They are very cheap, have a limited spectrum of action, and are
useful for treating the most common infections in the population.
Okay, so these are drugs that are used as a first or second choice. Agreed.
By the year 2030, the.
The World Health Organization has set a
challenge: 70% of the drugs used, of the
antibiotics used, out of 100% of the drugs
used, 70% must be in this category.
Oh, sorry, I've gone off on a tangent.
They have to be in this green category.
OK.
Then we have those in the yellow group, the yellow-orange
traffic light, which are drugs, antibiotics that are used in
serious infections and are first or second choice, but only in serious
infections.
They are worth certain things afterward, such as a nosocomial infection, for
example.
Okay.
Uh, its use generates a risk of resistance, so its use must be
restricted.
It is only worth using in specific situations
where it is described as working.
And then we have the banned antibiotics, okay?
Or those used as a last resort, the red light
antibiotics, which are reserved for infections
known to be caused by multi-resistant bacteria.
Severe nosocomial infections require ICU medication, a
valuable resource for intensive care units for bacterial diseases.
Above all, there are those that are acquired at the hospital level and whose
effectiveness must be preserved.
They need to be managed very well to be used only on those occasions.
They are expensive drugs with more adverse effects.
It is already known that there is bacterial resistance to these drugs.
Therefore, we cannot afford to overuse these drugs,
because if tomorrow they cease to be useful in these
serious diseases that can already cause the patient's
death, then this problem would worsen.
Well, within this color-coded traffic light system, a study of the
consumption of these drugs by these categories has also been done.
Okay?
So, we're going to meet the challenge of
having 70% of the antibiotics used
in 2030 be in the green category.
And we can see that at an international level, well,
we're there, we're not at 70% yet, but we're getting there together.
OK.
But what about the map on the right, the scheme on the right,
which is consumption in our country, in Spain?
What do you think?
Pretty bad, right?
I would say very bad, very bad.
We still have a lot to learn.
OK.
We've been getting by all these years.
The one behind the antibiotics in the yellow
category, as you can see here. Okay.
And those that are in the green category have to reach 70% by 2030.
So we have a long way to go to optimize the use
of these antibiotics and use them correctly.
Okay.
So what messages are we going to take home with us?
Boys and girls, you can start telling this to
your family, your friends, everyone, because this is the Bible.
Okay.
This must be strictly followed because we are all
responsible for the proper use of these drugs.
Well, they are only used for bacterial infections.
We've said it repeatedly, let's be clear: having a fever,
sore throat, pain, headache does not mean we have a bacterial infection.
OK.
What if we take unnecessary medication?
Well, these drugs also have adverse effects.
I don't have time to list them all, but they alter the microbiota, produce
allergies, and a lot of other effects that are not so well known to the
population.
Because they exist, because all drugs produce adverse
effects and antibiotics are no exception.
Well, they are only used under medical prescription.
Okay, this is very important because it's about people self-diagnosing.
He even goes to the doctor asking, ordering, that he be given an antibiotic.
Let's see.
Well, it will have to be the doctor who says if it's a bacterial
infection and if an antibiotic will be needed.
No? Okay.
The treatment must be followed correctly.
By the way, antibiotics used to be easier to get at the pharmacy without a
prescription;
now nobody will go to a pharmacy to buy an antibiotic because if you don't have a
prescription they won't sell it to you.
Okay, it's always with a doctor's prescription.
The treatment, the dose, and the duration must be followed correctly.
Because of those principles we have seen before, pharmacological, the form of
administration.
And this is important if the treatment is three pills
a day for seven days, because that dosage must be followed.
Okay, you have to follow the drug's technical data sheet
and take into account what time of day it is taken and with what food.
Some antibiotics can be taken with food, others on an empty stomach, and others
cannot be taken with dairy products because they are inactivated.
Okay, so there's a lot of fine print behind it before
we can carry out an effective treatment.
OK.
And what about adherence to treatment?
Never interrupt treatment.
It is true that after 24 hours following antibiotic treatment, the
patient feels much better, and the fever disappears.
Okay, the pain disappears.
But that doesn't mean we've eradicated the infection
and that there aren't any bacteria out there yet.
OK.
Clinical guidelines state that the infection lasts for seven days.
Well, it's seven days.
They are not one or two.
No matter how much I might feel improved. Okay.
And lastly, do not use leftover scraps.
This has also been mentioned before: do not self-medicate.
In Spain, we tend to keep any leftover medication in the medicine cabinet just
in case.
Well, in a month I'll have another self-infection that I
self-diagnose and go to the medicine cabinet.
I'm taking an antibiotic that will be incomplete because it's made from
leftovers.
I'm not going to do anything with him.
It will be completely inappropriate, ineffective,
and will encourage resistance or the emergence of resistant bacteria.
And in this sense, uh, this news that came out last
week and that Belén also mentioned earlier, the
Spanish Agency for Medicines has decided to change
the packaging of antibiotic medicines.
Because?
Because in the example I've given you here, an infection is
treated for seven days with three pills a day, seven times three would be 21 pills.
Okay, so the containers came with 30 or 40 pills, that's why we had some left
over and kept them at home.
Danger, danger, danger of abusing them in the future. Now
that clinical evidence has shown that the durations of
antibiotic treatments are being reviewed, the packaging
has been adjusted to the number of tablets that are actually needed for that
treatment.
So, let me give you the example of amoxicillin, which is the most commonly
used antibiotic, which used to come in packs of 30 and 40 tablets and now has
been reduced to 20.
Okay, so this new proposal that came out
in the news last week, well, it is a good solution, right?
By at least reducing the misuse by taking leftover
medicines from the medicine cabinet and self-medication.
Okay, then let's hope it works.
And to finish up, I'll end with Mr. Fleming's
prophecy, which he said in his Nobel Prize
speech and which was already known, right?
And he said it just like that, exactly as he said it.
The day will come when penicillin will be available for purchase by anyone in
stores and pharmacies.
Then there will be the danger that an ignorant man could
easily take an insufficient dose and, by exposing his
microbes to non-lethal amounts of the drug, make them
resistant, because 80, 80 years later, these words still
resonate, Vale, in this world we have, threatened by these resistant bacteria.
And that's all.
Thank you so much.
Uh. Next up, Alejandro K12, senior scientist at the
National Center for Biotechnology of the CSIC.
Uh. His work focuses on bacterial evolution and the mechanisms
that allow microorganisms to develop resistance to antibiotics.
EH has published in high-impact scientific journals
and has participated in international projects.
They are investigating how to stop the emergence of these resistances.
His approach combines evolutionary biology and experimental
microbiology, providing an innovative perspective
for understanding this phenomenon.
Today he will share with us some of his most recent
advances from cutting-edge research.
Good morning.
Thank you so much for having me here.
The truth is, uh, the task we've
been given is a bit of a nightmare.
I'm going to admit it because they told me I'm going to give an
informative talk about my work, but one that's also informative, about antibiotic
resistance.
And well, I'm letting you know that there will be high school students, there will
be
undergraduate students, there may be some PhDs, so it's like, excuse me, uh, what
am I basing this on?
So I want to start with a survey here.
Okay.
Uh. Could you raise your hand?
Those of you who haven't finished high school?
This entire block here. Everyone.
I'm a high school student, but this is the front row.
And what do you know about the last year?
Latest?
Okay.
Okay. And you're studying science?
Are there any who don't go into science?
Can you raise your hand?
The one who doesn't go into science.
More presences outside of outside.
Okay.
No no.
So now I'm coming back to you.
Now? Well, with us.
Here are the people who understand that they finished high school.
And here we have it. We have it.
How many people are doing the degree?
He doesn't have the pre-degree yet. Okay.
All science degrees. I imagine.
Okay, then the rest.
I imagine they're people working on their theses. Or higher.
No no.
Are there any people here who don't work
professionally in science but
already have a degree or work in education?
What do you do?
What do you do for a living?
English?
Well, don't worry because he has some things in English in the talk.
Okay. So, this is for everyone.
So be it.
You're a mixed bag. Okay. Fine, let's go. Good.
I'm going back to hang out with the people from high school.
Do you know what a Codon is?
What is a codon?
Let him dare to tell me.
Someone.
Anyone up for it?
What a load of crap it's made of.
There's one.
He's gesturing. You make the gesture. That's it.
This is a codon that contains DNA letters. No.
How many letters?
And what's the point of that? What information does it provide?
What training does it contain?
An amino acid.
Okay. Each codon gives you one amino acid. Good.
Very well. Okay.
I have more questions for you.
Do you know what an active center is?
Area of ​​any active center?
A biological context.
I'm not talking about a bank branch.
An active center of something.
An enzyme.
Here it is. It describes how an enzyme's active site plan
works, what happens in the active site of an enzyme.
Is there any activity?
Is there some kind of magic involved?
Is something happening in the active site of an enzyme?
You can tell me.
We don't know what it is. They haven't explained it to us.
It's one.
Have you never heard about incentives?
They consult with the person next to them.
Well, it's active. The magic isn't happening.
Okay.
This happens to the catalysis of enzymes that eat antibiotics.
The chemical reaction that destroys or neutralizes the antibiotic.
Okay.
Okay, I'll get started then.
Hey. Could you dim this light here a little?
Let's see.
No. How do I turn this off?
For someone else.
This is what the screens say, but I'll be here pointing.
I have two more questions before we begin.
No, what I really want is for her to know why I'm going to be pointing there.
This cannot be done. No.
Okay, no problem.
It's okay. Okay.
I have more questions here.
Do you know who this man is?
Well, a random guy.
Who?
Laplace?
Well no.
Well, he's finishing high school.
Who is this man?
Do you recognize yourself?
It's Darwin.
Okay.
Do you know what Darwin did?
It halts evolution. Okay.
Okay.
So the other question I had is whether you know who Laplace is.
Do you know who Laplace was?
Mathematicians and physicists.
Okay.
Okay, then, let's go.
Uh, this won't work.
This isn't going to work.
The date down.
Perfect. Okay.
Here we have Mr. Alexander Fleming, who has come up in practically every talk. Or
so it seems to me.
Uh, it's just that... One.
Penicillin. Okay.
Well, I'm going to tell you my story because it turns out that this
gentleman discovered penicillin at St. Mary's Hospital in London,
which belongs to Imperial College, the Imperial College of London, where I was a
professor.
So I've had to tell this story several times and I'm going to tell it again.
So if you can take a stroll around there, around Kensington, you'll see this
plaque.
Oh, sorry, I'm getting carried away.
It is said that Mr. Alexander Fleming discovered
penicillin on the second floor of this building.
Okay.
And the story has been told a thousand times and it is always described as luck.
What a stroke of luck this man had because he found penicillin.
This. Watch out, this. Watch out, very careful.
Okay, that's not how it is.
This story has been told many times.
It's true he was very lucky, but let's see, because we have to be careful
and I say this from experience, because when I first heard this
story, the normal version, Fleming was so lucky!
The first thing I did was call my mother and say, "Hey, this is going to be a
disaster."
Thanks to that, he found penicillin yesterday.
A Nobel Prize.
You've always told me I'm a disaster.
I think it's very good.
But it's not that simple.
Okay, it's not that simple.
Let's take it one step at a time.
First of all, he was lucky.
He was very lucky. Why?
Why has it been told here as well?
It has also been mentioned.
Here is the famous plaque where, well, a fungus was found.
How come your tomatoes grow when you leave them open?
It turns out I had put a bacterium here.
And here is a ring they called The Ring of Death.
Ring of death? Because no bacteria grow here.
Therefore.
In conclusion, the fungus is producing something that kills the bacteria.
Okay, because he was lucky.
First, because it's a bit of a mess, not because the lab is full of plates, but
because you shouldn't throw them away.
This plaque, by the way, I suppose this is not the original plaque, not the ship
in general, it was the isolated colonies.
And this is one.
This is a plate to make it look like almost a month ago.
The plate in the lab is growing. Okay.
Uh, it was about to be thrown away when a visitor
came to the lab and asked what she was doing.
And the man kept picking up plate after plate until he picked up this one and
said, "Well, look, the pollution has grown here."
What is that? It's a fungus, damn it, see if there's a ring of death here.
They're not growing. What's going on here?
In other words, he was lucky to have gotten that exact license plate.
She's showing it to someone.
In addition, the plate where I had bacteria contained almost a
bacterium called Staphylococcus, which grows much faster than the fungus.
Okay, this is a story that isn't often told.
How could the fungus have been growing there?
When the bacteria grow much more, the bacteria should have grown and not given
rise to it.
Well, it turns out that, uh, this plaque was growing
in the laboratory when there was a cold wave in London.
So the cold favors the growth of the fungus, and therefore
this fungus was happily growing there and was ready to be seen.
Okay, okay.
He was lucky.
But the.
The moral of this story is that being a disaster, being lucky, isn't enough. No.
And for this I always like to remember Mr. Louis Pasteur.
Do you know who Pasteur was?
Another great microbiologist.
Are you familiar with pasteurized milk?
Are you familiar with vaccines?
This is the man who did all those things.
Okay.
And Pasteur had this rather spastic motto that
says, "Fortune favors the prepared mind."
English teachers. Am I translating this correctly?
Yes, perfectly.
So this is key. Okay.
Being lucky isn't enough.
You have to be mentally prepared and then be willing to put your
heart and soul into things and make them happen.
Okay.
We get a Nobel Prize just for being a little sloppy at home.
OK.
Okay.
We continue.
It was already mentioned here as well.
But indeed, when antibiotics were discovered, they were a miracle
medicine, because suddenly a lot of infections that made
people's lives very miserable could be treated.
This is a poster that you will see in many talks of this style where they
advertised on the street: Hey, we have a cure for gonorrhea.
Gonorrhea, as you know, is a sexually transmitted disease that, if left
untreated, can spread to the rest of the body and make life very, very miserable.
For people.
What's happening?
Why are we here today?
Well, shortly after penicillin began to be
administered, the first reports of resistance appeared.
A few years later. Okay.
But it's okay, because we have a lot of people looking for antibiotics right now.
Okay, let's find another antibiotic. Okay.
A few years later, their meals appeared, which we then marketed.
There were some really cute little bandages for.
Thank you.
A wound or to treat the infection in just
a few years. Resistance appears.
Well, don't panic.
We're going to continue investigating. Looking for antibiotics.
Tetracycline appears.
It works very well.
A few years later, just a few weeks later, resistance appears.
Well, I think you've got the hang of it.
Basically, that's happened with every antibiotic we've launched. Right?
In other words, there are no antibiotics where you can say it's guaranteed that
there won't be resistance.
This is a losing battle.
There may be different opinions, but it's a battle that is truly won simply by
bringing out new antibiotics.
This is throwing money away.
And this is why people who have money don't want to throw it away.
He is escaping from it, which would be the company of Discovering Antibiotics.
Here I am showing you the number of approved antibiotics (Blue Line).
This would be the time from the 1980s to 2010.
And this blue line is the number of antibiotics that have been approved for
use.
The line is going down.
What does that mean?
Sometimes fewer antibiotics are being withdrawn.
And then here they are telling us.
In 1990 there were 18 companies with active
research programs in the development of new drugs.
In 2010 there were only four.
They're escaping, they say.
It's not worth it for me to invest a lot of money, develop a new compound, only to
have antibiotics appear immediately afterward.
I'm going to dedicate myself to what brings in the most money, like the Tempi
for example.
Or you know, it reduces obesity.
Okay, so now I'll introduce myself, uh, I work at the CSIC.
That is the Higher Council for Scientific Research.
So, I work in evolutionary biology with microorganisms, okay?
And one of the things we do in the lab has to do with antibiotics.
But I would never risk trusting a great authority on the subject of antibiotics.
I simply use this model because it is very useful, because
it is very necessary, and also because, for the things I do,
I also take advantage of all the knowledge that other people have
developed over time.
So, this is a bit of a new concept that I'm putting here again. This
gentleman here isn't Laplace, this gentleman is Darwin, okay?
The father of the theory of evolution is trying to recruit
people into his army to adopt an evolutionary view.
Say, "Hey, the problem of antibiotic resistance is something that just happens
out of nowhere."
It's not evolution in action.
Okay?
It's the survival of the fittest in action.
Okay, it's the giraffes whose necks grow because they're the ones eating the
leaves at the top the best.
It happens that here, instead of being the one who eats the top leaves best,
it's the one who isn't killed by the antibiotic.
Let's go.
Someone might say, "But this is the moment."
This sounds familiar to me, that evolution was something very slow and
gradual.
The word gradual is closely associated with evolution.
Because?
Originally, when Darwin wrote his great treatise, based on
his observations, he had this idea that came from geology
that, well, all processes take millions of years and are very slow.
Because?
Well, he did quite well, discovering the theory of evolution back then. Okay.
So, uh, yes, indeed, if you think about dinosaurs, extinctions,
trilobites, these things, it seems like things happen on
enormous timescales, but no, indeed, we know that evolution
can happen very quickly, especially in microbes,
viruses, bacteria, and fungi, right?
We're talking mostly about bacteria here, but they pass by very quickly.
Because?
Do they have anything special?
Well, they have some tricks up their sleeves, but elephants
and people do many of the things they do too, right?
For example, spontaneous mutation.
This is simply a.
It is an inevitable product of physics and chemistry.
Every time the 4 million letters that make up the genome of
a bacterium need to be copied, it has to be done.
That in less than 30 minutes.
Imagine what... let's see if I remember.
The analogy seems to me like copying the Bible 30 times in less than half an hour.
Imagine doing that by hand, you're going to make mistakes, right?
Furthermore, it's not just errors in the replication
machinery; there are a lot of endogenous and exogenous mutagen sources.
They're just words, so they seem very scientific, but it's to say, internal
sources.
When you are metabolizing glucose, the presence of
oxygen produces oxygen free radicals that are more
generic and break DNA and exogenous sources, that is,
they come from the external environment, which can
be radiation from nuclear bombs, but also alcohol.
For example, when alcohol is metabolized in the body it produces aldehyde, which
is also a gene.
So it's inevitable.
We cannot live without mutation.
Then bacteria have a very interesting little trick that I thought Jerónimo
was going to talk about in a little more detail, but it is that they are able to
exchange genes.
Basically, here we see this blue bacteria giving a little gift to the green
bacteria.
The green bacteria stares at it, eats it, and turns into blue bacteria.
It is becoming, it is acquiring that property. That phenotypic trait may be an
antibiotic prescription, it may be something else.
Thanks to a neighbor, an English teacher, who
passed on a gene, a package of genes.
This is for you. Thank you. You're a sweetheart.
I feel very strong now. Good.
More or less.
Yes. Okay.
Very good.
This is called horizontal gene transfer.
And that's a problem.
Okay.
Okay, the mechanics are very simple.
Pure Darwin.
Okay, you have a very large population of bacteria.
That's an advantage that bacteria have.
In a single droplet you can have millions of bacteria, millions of cells.
Therefore, the probability that someone made the
lucky mistake... We're back to the element of luck.
That error that changes precisely that amino acid in the active site of
that enzyme that is going to give you resistance, well, the
probability is much higher when you have 10 million cells.
So here I am putting the resistant bacteria, the one with the happy
mutation.
It is a large population, a vast ocean of cells that are sensitive to the
antibiotic.
What happens now?
The antibiotic arrives, kills everyone, and the
resistant bacteria remains, which now has it all the time.
Space and resources.
Food spreads very quickly. Okay.
This is a detail that is sometimes overlooked when one thinks about
how long it has taken whales to evolve from an ancestor that resembled a
hippopotamus.
What he's not thinking about is what we call selection pressure, selection
pressure.
Let's see if I can spend more time in the water, because there are little fish
here, nothing to eat me.
Well, that's an advantage you can take, but the selection pressure
of 'oh my god, they're going to kill me, I'm going to die' is much stronger.
And what does that mean?
If I get the beneficial mutation, I'll have no competition.
Then I can expand a lot.
So each evolutionary step happens much faster.
And this is why bacteria that are ingenious at producing mutations,
sharing them among themselves when we give them antibiotics,
are also able to adapt and evolve very quickly.
Okay.
In my laboratory, what we do is study these processes in real time,
we do experiments, a discipline known as experimental evolution,
and basically we make units of bacteria and see them under a
microscope, we study them with different techniques, we look at
their genome, we see what tools, what mechanisms they have followed
to be able to solve the adaptive problem that we propose to them.
In many cases, antibiotics.
Well, I'm going to tell you a story about a colleague from
Harvard University named Michael Bain, who did something fantastic.
You don't know what a Petri dish is, do you?
Does that ring a bell?
Where?
Where did Fleming find the fungus that was growing? No.
Well, Mr. Michael and...
And the head of the laboratory.
At the time he did that, he happened to make a giant Petri dish.
A Petri dish that they also filled with a kind of gel.
A type of jelly where bacteria can swim.
Okay. Good.
And what does that have to do with antibiotics?
The funny thing is that this is a giant Petri dish.
What they said is... Well, look at the edges.
Let's assume there are no antibiotics of any kind.
But then we're going to divide this land into strips and the next strip.
There will be an antibiotic concentration that kills the bacteria in the
next band ten times the concentration 100 and one thousand.
Okay.
And we're going to have a kind of competition, like when we used to play
tag.
I don't know if that's what it's called in Madrid.
If that's going to happen now, then no, no.
So basically the idea is I'm going to inoculate the bacteria on each side, on
each of the ends, and we'll see if they are able to adapt, to see who reaches
super resistance first.
This is the idea.
So here we have Mr. Michael inoculating a small amount
of bacteria, let's say coli bacteria, there.
As I was saying, bacteria, among many other things, are able to
swim, to swim vigorously when they have enough of a medium with sufficient low
viscosity to move.
Uh, what I'm putting here so I'm not just talking
to you guys, well, here we have a zoom of the flagellar
apparatus of a bacterium which is basically like
the propeller of an outboard motor powered by GTP energy.
This is spinning, or I knew it but hadn't forgotten it, but
at a very high speed and it allows the bacteria
to move over distances that are related.
They are on the order of millimeters to centimeters per hour.
Something that measures in microns is worth it.
Okay, messages bacteria can swim.
So let's see if they're really capable of winning this race.
I repeat once again how to say the design of experiments.
We have a large Petri dish with a very high concentration
of antibiotic in the center, inoculated at the
ends, and we're going to see what happens.
Okay, first I'm going to go through it a little quickly.
Okay? And then I stop.
Huh? The only thing you need to know is that you'll see this
little white thing here much better on these screens, for sure.
Okay, I'm going to put it here.
Okay. Here.
Do you see it? No.
And here you are. Do you see him, little white boy?
For contrast, we are in the zero antibiotic band.
So the bacteria is happy.
The inoculation begins to grow and also begins to swim.
And what happens?
Well, in a matter of hours it has already colonized
all these bands where there is no antibiotic.
But look how they're all lined up.
Nobody here dares to take a step, nobody dares to take a step.
Where is Mata's antibiotic?
They're all there, let's see who makes it to the First Division.
Okay?
Well, a little time passes and suddenly we find.
What's going on here?
What is this?
What's going on here?
These feathers are coming in.
And here they are in miniature.
Does anyone know what that is?
Again.
That some have adapted.
These are what we call mutants.
These are mutants. Every time, dear.
A mutation that suddenly allows them to live.
And to consume the resources in this territory that has antibiotics.
Look, this one here is super good.
Is it going at full speed, because this process happens at each of the
different barriers, they are all descendants of the same one, so
each mutation accumulates, the previous one and each one is worth it?
And well, finally they reach the end and we have almost, almost a tie.
I'm going to repeat it one more time: inoculate.
Come on,
They grow to the edge, the settlers begin to grow, and we reach the end.
Okay, so this experiment, what I just showed
you, took 11 days, that is, only 11 days.
These bacteria were able to learn.
Let's say, if you'll allow me, to resist antibiotic concentrations
a thousand times higher than those that already kill them.
Okay?
Here we are, witnessing in real time before our very
eyes this tremendous capacity to evolve.
Well, we're not staying here, are we?
We see that there are a lot of very interesting phenomena.
For example, we found, uh, let's give an example.
For example, what we're seeing here, right?
This species is like one of the diversifications that exist, right?
It's like suddenly several offspring of the same colony appear and find different
solutions, right?
Then you can see cases where it's not well known.
Forgive me, those of you on this side.
Here's a, let's say, a clone elbowing its way in.
Basically, it goes in. I don't know if you notice.
Then he elbows his way through.
It is. It's because it acquired a mutation later than the others.
But that mutation is great and it literally gets rid of him.
Well, the beauty of this work done in 1916 is
that, uh, they took samples from every site.
It was a bit like the phylogenetic tree of all these populations and
the sequencing, which allows us to also know what genetic changes are happening.
Not only that, but you can take the bacteria, you can measure its antibiotic
resistance, which has these colors, okay, and you can actually know how much
resistance has been acquired through which mutations?
And I'm just going to give you one example, this case here, okay.
The colors are a little confusing, but these arrows are purple, right?
They refer to what happens between this evolutionary stage and these
two children that this evolutionary stage has and its two children.
Okay? At this evolutionary stage, this clone already carried
all these mutations. It doesn't matter if I explain what they're
doing, but basically they're messing with the enzyme that's
being compromised by the antibiotic.
The antibiotics are blocking an enzyme essential to the bacteria, preventing it
from functioning, and that's why it dies.
Well, the bacteria just happens to make changes in the
sequence of its protein that presumably make it resistant.
The interesting thing is the two children. You see?
There are two cases, the two children.
One of them acquires a 4th mutation in the same gene.
Continue.
It continues along those lines of "I'm going to make this enzyme."
Nobody's going to touch it. Okay.
But there is another one that, as you can see, is
acquiring a mutation into a little thing called Mar.
Ah, that's good, well it's a good regulator,
it's a gene that has to do with the general stress response.
This is a gene that, when activated or touched by bacteria, suddenly says, "We
are dying,
we are going to start expelling everything we don't understand that is
around here."
Any toxic product that is suspected of being toxic will be tested with pumps
that have bilge pumps.
Like the water girls, there's everything outside.
We're going to close all the doors.
Okay. Bacteria have doors to get in. Stuff.
They have sentries there who allow them to enter or not.
They say, "Let's shut everything down."
We're going to expel everything. Let's see if we survive.
So here we have, in a matter of hours, a diversification into different
strategies.
Do you think there might be any long-term consequences
between one strategy and the other?
Have you already put a clue there? No?
People on this side can also answer.
It reproduces.
They are saying something very interesting here: These mutations can
have a physiological cost.
They can make it grow better or worse. And there are many examples of that.
But I don't know what I'm saying to you.
What I want to focus on right now is that we have a mutation that
continues the same line of making my enzyme invulnerable, and
another mutation that says, "Hey, look, what I'm going to do is
put into action a stress control system due to damage from compounds."
What consequences could this have in the future?
I'm calling here.
This right here. I'm calling it general strategy.
Excuse me, Specialist.
So I get better and better at resisting this single antibiotic,
whereas this strategy here will give resistance, as they
prove in the article, to other antibiotics, so by making you
resistant to only one at once, it makes you resistant to others.
Okay.
Well,
I continue because I'm afraid I'll run out of time.
This type of experiment allows you to ask many questions.
Another thing I want to talk about here is what happens when we play around with
these gradients a little.
So, what are we going to do in this game now?
It's a real experiment.
What they wanted to see is Vale.
The goal is to reach a thousand times the resistance.
It's worth a thousand times the resistance.
And we're going to inoculate here at these two points.
Because?
Because in this way we will be able to see if it is possible
to reach the same speed in a single stroke or
through increasingly smaller increments.
For example, here days zero, ten zero here days zero, 1000
and here you would go directly zero thousand okay.
And the same kind of movie.
At first, the bacteria grow happily in the area without antibiotics.
We immediately began to see these mutants invading and colonizing this new
environment.
And what you're going to see is that the path that
goes through the low intermediate concentration
of one is the first to reach a thousand.
I'm going to repeat it one more time. Okay.
The goal is to reach a thousand.
Who will reach 1,000 first?
The descendants of what was here. Why?
Because they've had a kind of shortcut.
Or a trampoline or a bridge, whatever you want to call it.
That intermediate concentration.
And that's the message of this slide.
Intermediate concentrations are facilitating this evolutionary process.
Because?
Because of a tiny concentration.
I'm selecting a tiny mutation that might give me a little bit of resistance,
and maybe mutations that give a little bit of resistance.
There are many more mutations that confer significant resistance,
but once I take one step and become a little more resistant, it
becomes easier to take the next step. Okay, because this is important.
It's something that's been discussed here too.
You can imagine that in the environment we have many
situations where there are very small concentrations of antibiotics. Okay.
Antibiotics are being given, huh?
It's not just in hospitals; it's being
given to aquaculture, to farm animals, and to our pets.
All of that is also eliminated when you go to the bathroom.
This is giving antibiotics and going down the toilet.
Okay.
So all these low concentrations of antibiotics appear in a lot of places.
And what this experiment is showing is that these low concentrations
act as a springboard to high resistance.
Message again.
Antibiotics should be used with caution.
They must be eliminated knowing exactly what is being done.
Okay, and its industrial use needs to be closely monitored.
Okay.
Okay, I'll continue.
How am I doing on time, or just badly?
Okay. Very good. Let's go quickly.
Uh, you have up to 20 minutes.
Ah, okay.
Well,
Okay, let's go.
More than enough.
Well, so I was talking about experimental evolution.
I've told you about a case that's very visual, but there are several groups
around the world doing experimental evolution for different things.
Okay.
I'm going to give you another example that has to do with the use
of this experimental evolution to look for weaknesses in antibiotic-resistant
bacteria.
So, in this work, uh, it's done by the group
that still values ​​the colony unit more?
What they do is an experimental evolution of hundreds of mutants.
It's not as we say.
I don't know how to say it in Spanish, because saying
"disruption" or "deletion" doesn't really clarify things.
Mutant, isn't it?
Cat is a mutant in which we have removed an entire gene.
Okay.
And so?
Well, it's a very laborious job that, fortunately for them, was done by some
Japanese people years ago.
There is a collection of bacteria that have all
the genes that can be deleted, deleted.
And these people took the genes.
What did you think?
There are these genes that are certainly important for bacteria to be able to
resist antibiotics.
We're going to test each and every one separately.
We're going to do an evolution with the idea
of ​​finding out if there's a key gene.
Can you imagine if we found a gene that, when removed, prevents bacteria from
evolving?
Hey, that's fantastic.
There's a target for a drug. No.
So this is a bit conceptual.
The idea is as follows.
We have a collection that is not going to be homogeneous because each one is a
mutant.
There will be.
They are mutants of important things, of regulators, of physiological, metabolic
things.
Therefore, they have a diversity of initial resistance.
Okay, they do the evolution and then they measure how
much they have evolved, their capacity to evolve.
And they also find that there is variability and they
also find a rather interesting relationship.
This is of great interest to physicists because
we have a kind of delay here in the power law that
tells us that the more resistant you
are initially, the less you adapt.
It doesn't make intuitive sense if you have it.
If you're really bad, then you have a lot more room to become good. That's not
fair.
But the goal is not to find a gene here.
It's okay that it doesn't evolve much.
This is evolutionary increase.
Okay, these genes here don't evolve much, but they were already
quite resistant initially, so there's not much I can do.
The goal is to find this gene out there.
That would be the perfect solution.
Okay, we have a gene that when you remove it I have no resistance,
it's very low and I'm not able, I'm not able to adapt.
Is this possible?
Well, as you can imagine, that's exactly what they find.
They find this gene by agreement that codes for one of
the most important units of one of these
expulsion pumps that I mentioned earlier.
These pumps remove all the toxic products that are inside the cells.
So this pump here is essential for power.
It is the first line of defense that bacteria have against toxic products.
When you eliminate it, it turns out they are unable to adapt.
Because?
Because one of the ways of adapting that they found here
has to do with improving the ability to expel things.
Okay.
Coincidentally, we also know of drugs that
are capable of inhibiting this, this, this pump.
Therefore, what they propose in this work, and in subsequent
ones, is the use of this type of drug as an adjuvant.
So, something that helps the antibiotic, because I give you an
antibiotic that I know you're going to become resistant to through
this mechanism, and I'm already preventing it, okay?
This is applied evolutionary thinking.
Anticipating the enemy's movement is worthwhile.
Continuous.
I'll give another example.
Same type of same type of experiment.
It's worth a lot of different mutant replicas.
In this case, instead of using a lot of genes trying to
find the key gene for resistance, the approach is to
always evolve the same strain to a lot of antibiotics,
to all the ones that are interesting.
Okay.
And I'm going to study when they finish.
If there is an antibiotic.
For whom resistance weakens you against other resistances, this would be
tremendous.
That there would be a give and take.
I don't become resistant to the antibiotic and I become more sensitive to
B.
That would be very interesting.
Well, this is what they find. Okay.
This.
This is called a heat map.
I don't know if you've ever seen it, but I'm going to explain it to you.
It's a matrix where I'm putting all these names.
They are antibiotics.
Okay. Me too.
Caffeine, gentamicin, medicinal cannabis, ampicillin, amoxicillin, EpiPen.
A lot of names you don't need to know.
The antibiotics here are telling you what you've
done computer evolution to on this side.
Here they tell you what evolution has become.
Okay.
At the top I'm going to do it in the middle one, at the top they
are measuring cross-sensitivity or cross-resistance to the same antibiotics.
Okay. So, in the example I gave you above, I make my
evolution to my little house, okay?
And now I measure those tough bugs.
If they are resistant to all these things, Azulito means that he has become
sensitive.
Rojito means that it has become resistant.
Hey, with promising medicine we have a lot of antibiotics
to which becoming resistant to caffeine makes me sensitive.
We can repeat this with all the combinations and
we find groups in these blue areas.
These are weaknesses that could be exploited.
OK.
I'll mention this too, Jerónimo.
What are called collateral sensitivity strategies.
Very good.
Cross-sensitivity.
Okay, so we now have two strategies based on this
evolutionary thinking that could help us. Great.
And now, I suppose that in the four minutes I have left, very briefly, I'm
going to
tell you what I do, because until now I've told you what others do.
Okay,
So, as I was saying in the lab, we mainly work on
fundamental theory, we work on having an
evolution with a fundamental approach.
We want to understand how antibiotics work.
It's an applied case that interests us a lot, but our real focus is on
understanding
the mechanisms and, above all, on understanding this question that's here.
Can we predict if we work on predicting evolution?
Can evolution be predicted or not?
Is it a completely random process or are there certain patterns that repeat?
We don't know.
So there's an experimental model where we work
a lot, it's the beta antibiotics, folks.
Summary of this Beta figure.
It's penicillin.
Okay, here's Mr. Fleming once again with his penicillin.
OK.
And you'll see that new and new compounds have been discovered in this family over
time. Okay. So.
We have a very large family. Antibiotics.
What's happening?
In hospitals.
Well, this is going to happen.
Well, we have bacteria that are resistant.
Not because they have acquired a mutation somewhere, but because they have acquired
an enzyme that eats the antibiotic.
These enzymes, called beta, have a property that,
in many cases, they also eat several things at once.
So, they're not just giving resistance to one electronic beta,
they're giving it to entire groups of beta lactase, which is a problem,
huh? I'm going to tell you about a project we've done with PC2, which
is the name we give it, but well, we didn't come up with it.
What can you see here? It's increasing, okay?
These are cases of bacteria that have developed this
type of resistance over time, from 2003 to 2013, and
you can see that it's increasing a lot, right?
A lot of people are working on this.
We know that there are a lot of mutants that appear in hospitals when
people sequence, and we already know what little things are changing
in those enzymes to make them more efficient at eating the antibiotic.
So, what we're proposing is, well, let's imagine that we
could take all those mutations and recreate them in the
lab, take the ancestral enzyme, put in the mutations and
then start combining them instead of the ABC mutation.
Then we have the double mutant A, B, a, C, a D.
Okay.
And this is where Mr. Laplace comes in.
It's a little late to introduce it.
But hey, that's live TV for you.
And now, Mr. Laplace, there was a physicist and mathematician
who said this thing in 1814 that is known as him.
This is the epitome of determinism, isn't it?
At that time, physicists were very proud because they believed they
understood the entire universe, and this gentleman said the following:
"If we were able to know the position and momentum of every particle in
the universe, if there were a being capable of doing that."
This is Laplace's famous demon.
Could we predict the future and also reconstruct the past?
This idea that the universe is entirely mechanical.
Nothing escapes these kinds of rules.
Okay, so let's do the same with mutations.
We're going to take the enzymes, introduce the different mutations, and
see their combinations.
So, if the world were kind, if the Universe were kind to
people, we would expect things to be simple and that.
Well, maybe I have a mutation that is very good, a bird that is a little
worse, the C is regular, the B is so-so, and when I combine them they more or less
follow the logic.
The best combination is a, B and so on.
Okay, so these are the experimental data we have with this enzyme.
And well, okay, we found an enzyme, a mutation that is very good and
another that is very bad, which is B, and then two intermediate ones.
So, as I was saying, if the universe were kind,
this peace demon, uh, could succeed.
What would we say?
We would say, "Well, the best double mutant is going to be the one
that combines A, the one that's sure to be there because A is the best,
and then it would have to be combined with C, the real one."
Okay, so the way we do the experiments turns out that no, it turns out
that the best double mutant is BC, that is, the worst mutation you
could see at the beginning was combined resistance with C.
What's going on here?
Okay, this is what is known as the phenomenon in genetics.
The clues are genetic interaction, as I've put there.
That's why the nearsighted demon can really see very little.
The reason for the clue transcends what I can tell you in this talk,
but we know because in the end you have to think that these enzymes are
dimensional entities.
Any mutation you make here could be interacting in a completely crazy way
with something over there. Okay?
Because this is interesting, because it's important for the things we were talking
about.
If I measure the cross-resistance or cross-sensitivity
of these different mutants to inform people who are in the clinic.
Listen, when you have a patient with this bug, give them this other antibiotic.
If I let myself be guided by the intuition that the best mutation
will be the best of a mutant, it will be the one that carries the
mutation to, well I would say okay, this is its profile
which is very blue, come on CTX, let's give it CTX.
But be careful, because you can also go this other way.
We don't know, we can't do anything, we don't know for this,
for this case we couldn't tell anyone what antibiotic to use.
However, since we have this phenomenon, it turns out that the
predictions are not what we expected, and we find an
unexpected double mutant and this double mutant.
In this specific example, it turns out that it would be very sensitive to
acidity.
Okay, this is just to illustrate, because this
unpredictability is ruining our promise of
being able to exploit cross-sensitivity.
And the very, very last thing I'm going to tell you is that all is not lost.
Okay, all is not lost. Why?
Because we have something called biases.
Mutations and it means bias.
Mutation means that some mutations are more likely to happen than others.
And why does this help us?
Okay, first I want to tell you the following.
Imagine that the sequence, the key codons are determining
the resistance of your enzyme, well, there is this sequence that is there.
Okay?
Well, I'm telling you that under certain environmental conditions
X where there is a mutagen, then changes from tea to C will be beneficial.
Well, I can tell that in this case, in this sequence of my enzyme,
I'm probably going to have this mutant, the tea by faith.
But if the environment changes, it turns out that the mutations
that are most likely to appear will be in other places.
They may be coding for different amino acids and therefore for different
enzymes.
Because this is in our interest.
Well, because we can go from a situation where the clue is
shrouded in a fog that we can't understand, we can't predict
anything, to a situation where we're putting Laplace's
demon glasses on and saying, look, it turns out that these
very powerful selection pressures, which would be these
lines that I'm putting in purple, regardless of which
mutation, which combination is better than another, are
driving evolution along different paths and, for example,
in this case, it would be leading us to a solution, which would be B, which wasn't
foreseen before.
Okay, so we hope that understanding and
mapping these computational biases will
allow us to counteract this unpredictability.
And with this
I am satisfied.
You keep saying that pharmaceutical companies don't want to invest because of
the issue of antibiotics.
But that's happening with vaccines.
Vaccines are changing every year.
Vaccines lose their effectiveness from year to
year, and antibiotics can last at least five years.
So I don't understand why pharmaceutical companies invest in vaccines but not in
antibiotics.
It was a rather general question.
I'm more certain that there's someone here who knows more about these kinds of
topics than I do.
But I have a relatively easy answer: producing antibiotics
is much more costly in terms of time and effort than producing a new vaccine.
The vaccine.
Is it enough for you to simply expose your antigen to the model you use?
Yes, that's good. We have to work.
I'm not saying that making a vaccine is incredibly easy, but finding new
antibiotics
is like searching for ants inside volcanoes, literally, and it's difficult
to
find them because not only does it have to be new, but it also has to be from a
different
family than the ones that already exist, because there can be
cross-resistance and they may not have hepatotoxicity.
Finding new antibiotics is much more complicated.
Thank you so much.
I'm playing devil's advocate here, because it's true that at the closing
of Micromundo we have often invited pharmaceutical companies to tell us their
side of the story.
And yes, it is true that of course it is not worth it for them, and what they say
is that they are not nuns.
But for example, we, a large part of the funding for Micromundo so that we can
reach so many institutes comes from MSD, and they have a social program, let's
say, where they do allocate money to the factory, to the production of new
antibiotics, because obviously it is much more profitable for them to do something
else.
But what the pharmaceutical companies are asking for is a little support
from the State to say, "Hey, let's do combined programs where we can do that."
So it's true that it's obviously a company.
Companies want to make money, but they ask for some support in that
regard, and they do have some special programs, which are kind of
a social purpose in order to develop new antibiotics.
But of course it's a business.
If you ask me.
Okay, so next up, to close the presentations, we have Cristina
Teixeira, Cristina Ballesteros, Laura Villar and Luisa
Botín, who are professionals involved in the development
and implementation of the National Plan against the Antibiotic Resistance Front.
The plan in the field of animal health in Spain has been
fundamental in the implementation of surveillance strategies.
Reduction in antibiotic use and awareness in the
veterinary sector have contributed to positioning
Spain as a leader in the application of the integrated
approach to health, human, animal and environmental health.
We were invited to reflect on misconceptions and inappropriate
practices in the use of antibiotics, allowing us to recognize
our role in this challenge and understanding that we all
influence both the problem and the solution.
Hello, everyone.
Uh, well, I started saying, "How are you all?"
Are you excited?
And I've noticed that you've already had five
talks and very few of you have slept.
Some of you have even removed notes; you haven't
looked at your phones just to take pictures.
Does that mean you like this topic?
Aren't you worried about antibiotic resistance?
She says no, that he's worried about holding her hand.
Aren't you worried about all those five, uh,
brilliant presentations you've had from
scientists who've explained what this is all about?
They conduct their research.
You're not worried.
Are you using antibiotics correctly?
Yes or no?
Raise the hand you don't use.
Someone who hasn't used antibiotics properly.
Well, but I see this is from the microcosm.
They're infecting you with this,
uh, problem by explaining what it
is, looking for solutions.
And then that's already a little bit like
messengers of what we want. That you carry.
Okay.
Today we're going to have a chat.
You've already had five. We've already explained everything about antibiotic
resistance.
You already know everything.
Now we're going to give you a test.
Okay.
Yes, yes, yes, yes.
We need to know what it is.
The messages you are taking from here
today that we want you to spread.
Why don't you use antibiotics properly?
Okay,
So, I don't have a remote.
Sorry.
First, I'm going to tell you what we do.
Who we are.
And to tell you who we are, I'm going to explain it in this very simple way.
So far you have had five people.
Super-enthusiastic scientists, those
we call lab rats, who, as Gerónimo has so
aptly put it, are opening up that knowledge
gap, lengthening it so that we can better
understand this problem, find solutions,
seek new therapies, and ensure that
antibiotics continue to work.
Us
We are office mice and we are on the
other side, in the administrative
part of government entities,
ministries to look for laws, measures,
tools to be used better in practice,
antibiotics less and better.
Okay,
We are the plan.
I am a Christian, I am a veterinarian, I
have my partner Cristina, who is.
I am also a veterinarian.
Laura.
Hello.
I'm a pharmacist. A pharmacist?
And Luis?
Or also known as Bubi?
No. Come on.
In other words, we are either three veterinarians or a pharmacist.
For every pharmacist, we need three veterinarians.
No, it's not like that.
Well.
And so we, on the administrative side, are looking for solutions.
Okay.
Do you think the problem with resistors has an easy solution?
Yes or no?
Come on, we need more cooperation. No.
Actually, I'm going to tell you yes, it has an easy solution.
And Girona has already spoken.
Yes. The problem is that we use antibiotics too much.
Well, they're used less and better.
That's it.
That's the solution.
What we need is a change in behavior from
everyone to use these medications less and better.
Okay, but
That's not easy.
The job is a.
It's not easy because, as you've
already seen from the previous talks
first,
The concept of resistance is not easy to explain.
It is not easy to understand, and
then it is not easy to solve and
implement, because as has already
been said, bacteria do not find borders.
This is not just a human problem; it is a problem
that involves animals and the environment.
So, in this thing we call the good Geoff, where we are all connected, there is only
one health.
So, a priori, it's not useful or not
It's the solution
Implementing measures in only one area of ​​Los Angeles,
when what we need to do is involve everyone.
And this implies forgiving
redundancy to many people.
It's worth working with a lot of people.
Okay.
So here's the plan.
The plan has been in place in Spain since
2014 and its aim is to implement measures
to ensure that antibiotics continue to be
effective or to curb this problem.
Okay.
We work.
You've already seen.
Veterinarian pharmacists work together on the aspects of
human health, animal health, and the environment.
And also
From a small team that you see here in the photo below, which
works exclusively for this, within the Spanish Agency
for Medicines, within the Ministry of Health, ten ministries collaborated.
70 scientific associations or societies and
more than 300 expert collaborators in this field.
In other words, what we do is connect all
these people, seek consensus, and put
measures in place to use it less and better.
Antibiotics.
Okay.
We work on strategic lines.
Okay. And I'm going to explain briefly.
First, surveillance.
It's important to understand the problem, to
know how much resistance there is.
And to know how many antibiotics we consume.
That's what surveillance is for.
After that, it's important to control the problem.
Controlling the problem involves implementing
measures, laws, signing agreements, and documents.
Prevention is important because part of
the solution is not using the least amount.
Better to apologize is to use them less and use them less.
It's about prevention.
Infections. Okay.
It is very important.
Then we did.
It's a problem of social change, of behavioral change.
We need many communication campaigns, a lot
of training, and we need the five scientists
or university professors who have been here.
We need research, to better understand
this phenomenon, and to find solutions to it.
The investigation.
Okay.
And now we're going to do the test.
Okay.
We're going to share a series of myths about bad
practices, how we misuse antibiotics on a daily
basis, and we're all going to discuss them.
Okay, so it's for you.
So I really want you to raise your hands and really participate.
Okay. The first one.
Let's see,
This boy who tells us.
I don't use antibiotics, so this problem doesn't affect me.
What do you think?
He is wrong.
I bet someone has already found a guy like this.
I, for example, have a brother-in-law.
I have a brother-in-law who thinks this doesn't apply to him because he takes
antibiotics.
Very good.
What should we say to him?
Anyone dare?
Come on!
I've woken you up.
Look, nobody's asleep anymore.
Does anyone dare to... we have here?
What would you say to him/her?
That antibiotics can learn to teach other people.
I mean, antibiotics first.
Yes, you'll use them at some point in your life. Yes.
And you can always help others learn how to use them.
Sure, but. I mean, this.
I don't use antibiotics, so this problem isn't going to affect me.
Exact.
I mean, because we've already discussed here that it's a problem.
Wenger is a collective problem,
and bacteria have no borders.
In other words, even though I'm doing very
well, a bacterium from someone who I know
thinks I take them badly can affect me through
direct contact, or through contact in
hospitals, the community, or through food,
or through contact with animals or the environment.
Even if you take it well, you can come into
contact with that bacteria and that becomes a problem.
In other words, resistance is like
infectious diseases are social diseases.
We already know what's going on.
COVID doesn't count.
So this is the message you need to convey.
It's not just what you do, but what we all do.
Okay.
I'm going to pass the word on to my colleagues.
Okay, I'll continue with this.
Okay, let's move on to the next case.
Okay, now that we've warmed up with the first one,
let's see what you think of the next
case we have to discuss together.
Okay, so imagine that we have a process or we are sick.
We went to the doctor and the doctor prescribed antibiotics
because we have an infection, and well, we have to take
the treatment for ten, 15, or 21 days.
As you know, as has already been discussed here, it depends somewhat on
the process
we have, on the type of bacteria where the infection is located.
But what happens is that when we start antibiotic
treatment, after a few days we start to feel better and
then we might start thinking, well, since I already
feel better, maybe I don't need to take it until I finish,
or we might even be tempted to stop the treatment and think, well, that's it,
huh?
So, my body won't get used to the antibiotic,
or I won't have side effects from stopping
it, huh? It seems like that's not the case.
Huh? So what?
So we would have two options, huh?
We could.
We would have the option of taking it until the end, or since I'm already
feeling well, not stopping taking it, and that way I'm taking only
what's strictly necessary because I'm already well.
So the question we have now is what do you think, huh?
Huh? What do you think we should do?
We can stop without problems because I already feel well, or would you
continue, uh, taking the treatment following the guidelines prescribed by
the doctor?
Eva explained this to us very well.
Yes of course.
Very good, very good.
What's your name?
Well, as it already is.
What happens, what happens when the treatment begins, is that
the antibiotic starts killing those bacteria that are most sensitive.
But if I interrupt it before finishing it, resistant bacteria will
remain, and when the treatment is completely stopped, those are the
ones that will stay, and then we have already created a problem.
And this connects with a very important concept that we have encountered
many times, which is that, uh, there are many people who think that by
taking the antibiotic it is the person who becomes resistant, but it
must be emphasized that it is not we who become resistant to the antibiotic, but
our bacteria, uh?
And those bacteria, as we have already seen, can be transmitted.
So it's important, uh, to follow the treatment plan.
If they have to leave, I don't know.
In other words, we can continue, it's no big deal.
Hey?
Well, that's all for now. Nice to meet you.
Well, you all got top marks, because I can see you were all paying close
attention.
No, nothing happened. Don't worry.
If it was just because it wasn't like this one.
I'm saying something very boring.
It's okay, it's okay.
Peaceful.
Okay, that gives them time.
And now we move on to the next case.
This has been antibiotic resistance.
The exams have this at the end.
Clear.
Let's put on the pressure and move on to the
next case, which is social pressure.
Okay, so another typical case is when I go.
Okay, I'm going to the doctor. I think I have an infection.
Okay, it may happen that I have an important event or not, but I think I do.
I think that because of the symptoms I have, I have identified it with something
that has
happened to me before, that I have had before and I was prescribed an
antibiotic.
I am waiting for the doctor, after the examination and after I
tell him a little about my history, to prescribe me an antibiotic,
and in this case we have also told him that I have an important event.
What I want is to feel better as soon as possible, okay?
And then I go to the doctor.
What he tells me is that, based on the symptoms and the
medical history, he or she considers that I have a viral
infection and that I do not need antibiotics.
And then?
Well, that's where it connects a bit with needing to feel better as
soon as possible, and also in this case, well, I went to my father, my
mother, I heard them and I said, but aren't you going to prescribe me an
antibiotic?
I think I'm sick enough without needing a prescription.
And also I think I've had a bit
of a fever, etc. And so here we are.
The question was a little...
We know that in this case, if the doctor tells me it's viral, then based
on everything we've seen, an antibiotic shouldn't be prescribed, but
the question is whether you think it's worth it just in case.
But I also think, okay, even if they tell me it's viral, I know I might have a
bacteria, because I think so because of the symptoms and all.
And then, uh, I put a little pressure on the doctor to prescribe
that antibiotic because I really think I need it.
I don't know if anyone has been through that situation or not.
Yes, tell me. Yes
preventively.
Yes, but there are reasons for that.
In other words, there are high-risk clinical cases when you go into
surgery where they open you up with an incision in the operating room; that's a
lot of risk.
You have to have one.
A preventative antibiotic.
But.
That's a common clinical practice that many dentists have.
But anyway, I'm speaking on behalf of Human Health.
Do we have guidelines for prescribing antimicrobial treatment in the
community that include oral and dental infections, because, as Cristiana
says, there are infections where antibiotic prophylaxis
is necessary due to the risk of the infection itself, right?
I don't know if you're familiar with endocarditis caused by dental procedures,
but there are many others that you're not, but what the general public
remembers is that we need an antibiotic.
If you have a tooth pulled.
So what we're trying to do here.
The talk was also somewhat focused on the topic of students, awareness,
but we work a lot on raising awareness among the population, because
it's not just what professionals do or don't do, what we investigate
or don't investigate, it's also what the population already has in its DNA as a
society.
This is what is being talked about and done.
And if you don't send it to me because he's a bad
professional, then we're also trying to change that.
Another problem, yes.
Yes. Our dad, look.
When the port arrives, I see him, I thank him because he has no antibiotics left.
I'll see if it works for me.
I believe.
Another question.
In the end.
So it seems that no matter how much I tell them everything
since Monday last time, I think there is a.
There is pressure and I think there is a lack of conceptual understanding
that we should already have that person vaccinated so that we know we are
there, because if you are not asking for a sacrifice that also has to do with
yourself, well, okay.
But we get nervous around small children, right?
It's inexplicable.
In fact, that's what I was going to say, that this problem of
pressure is especially pronounced in children, because
there is greater pressure to prescribe antibiotics, and for
that reason one of the lines we are working on in the plan is to
develop guidelines in which the doctor has a clear decision
tree to see when to prescribe antibiotics and when not to, having a ten-year basis
to rely on.
When you have these questions that I'm talking about.
Well, we also have campaigns in the plan.
Of course, the pressure to prescribe is one of the
problems because more antibiotics are prescribed
than should actually be prescribed.
Okay.
That's all that's left.
Now.
We're doing something right with the plan.
We're doing something.
TRUE.
Yes. Yes, there are.
There is another measure that is not yet implemented because it is very difficult
to implement, which is called deferred prescription.
Delayed prescription means that the doctor prescribes an antibiotic
and you leave it to your responsibility to take it.
The system kind of unlocks it for you after a few days so you can get it.
The problem?
There is no rapid test for all bacteria in the office, so of
course, but a culture is not viable in many situations
because you don't know which bacteria you have.
It will probably take longer to take him to the hospital, the
culture, the return and the result than to give an empirical
therapy that charges you in case it is suspected to be bacterial and not viral
as well.
What we do have are more rapid viral tests, but for what?
To confirm it, to say, "Hey, look, I haven't confirmed that it's bacterial,
but I have confirmed that it's viral, so you can't take it."
And then there's also an environment where the sampling is different,
there may be more contamination, you take it to the lab, a thousand
things grow and you don't know if you want to, if not, what to do.
You give a person who is in the community with a crop that you believe
has contamination, a 4th generation cephalosporin.
Well, it's a little bit uncertain.
Of course, if it gets worse, if it goes further, that's when we have to go to the
hospital.
Are there also clinical criteria in the pathways where the primary care physician
refers you to the hospital, and why?
Because that infection is considered to no longer be treatable in the community
with community resources.
If you need to have a bronchial wash or any other more invasive procedure, you
need to be taken to the hospital so that you can be treated in the best possible
way.
That's why there's a middle ground, and also delayed prescription, but I'm
telling you it's very complicated because it depends a lot on the patient.
I also have an 18-month-old baby and it's extremely difficult.
In other words, I've managed to stick with the three-in-one recipe for four
days.
Because?
Because I say, I don't know if it's conjunctivitis in my son; in three days
he hasn't improved. They give
it to my poor son and he wakes up with so much eye discharge that he can't open his
eyes.
And I say, well now it does cost, it costs a lot, it costs a fortune.
No, I mean, I don't know if there's been more
awareness in recent years, but doctors
themselves weren't as up-to-date a few years ago.
With all the problems surrounding antibiotics.
And yes, the doctors themselves end up not raising awareness
properly because they are not up-to-date, the population cannot
keep up-to-date either, and in the end the population depends a
lot on the opinion of a doctor or what a doctor says, sorry, a doctor, a nurse, a
specialist.
And if the specialist is not informed, that's one thing, and then another.
the topic of
of the crops and such.
So I think it takes a long time for a day to grow.
What grows.
Choose a colony, identify it, and see if it is resistant.
It takes another day, and by the time you want to see it, you're already in very
bad shape.
And the time it takes to get the remedy they can give you isn't worth it, because
the antibiotic will be the same, the one they'll be giving you until the culture
comes back.
So in the end, sometimes if you were quick to get strep throat for
tonsillitis, it's
worth it, because it's proven to be the bacteria that most commonly causes
tonsillitis in the community.
So there are certain things that we do know and others that escape us, besides
the
fact that many bacterial infections are also self-limiting.
I mean, it's not that they all, absolutely all, need anti-therapy.
That's why there's also the level of observation time.
You have what everyone has.
Well, let's see, let's wait and see, it's not about delaying it just for the sake
of delaying it.
My husband often tells me, "I take it just in case, you know, 'the shoemaker's
children go barefoot,' but I take it just in case, because what harm can it do?"
Well, all this, all this.
We have to explain what happens because when you experience
it firsthand, it's very complicated, very complicated.
Just a quick thing.
When I was in the UK they had something that sounds familiar to me, this
delayed prescription thing, because you'd go in with a urinary tract
infection and they'd give you a generic thing and take the samples and
two days later they'd call you and say take this or take this other thing and
we'd put it on your card.
I mean, I don't know if it was at the level of the entire health system, if it
was a pilot
program, but I remember when they were doing it in Sweden and here they are
really trying to fine-tune it, right?
And now that we're here, the university working sector, there's
something very important: when you affect the pockets of the
State, those in charge, then a delayed prescription has proven
to be one of the most cost-effective measures, along with prevention, to
prevent resistance.
So, all that stuff he does, hey, I want this deferred prescription.
In fact, deferred prescription is within the basic portfolio of
the National Health System, that is, it is included as a service,
but it is very difficult to implement systems.
I'm going to tell you about our troubles because we're going to cry at the
bookstore, but it's very complicated in many ways.
There is no risk, there is no risk with that type of prescription that it is.
So after four days, if the person is not feeling well and then feels well, they
also take antibiotics to have at home.
Given the obsession that exists, I'll take it anyway.
Yes, there is, absolutely.
Ultimately, it's like offering the option of having a backup
antibiotic, but the difference is that in this case, you leave the
consultation with a delayed prescription or with a prescription already written.
So, with delayed prescription, there are a lot of studies.
In fact, a few years ago we sent it to the Health Technology Assessment Network
to do a literature review of all the scientific evidence that exists for the
use of delayed prescribing.
And there is a percentage that improves, that improves, not all, obviously,
because in the end many relapse, but compared to going out with the prescribed
antibiotic, well, going out with it is not comparing it with not prescribing
because not prescribing is because you firmly believe that it would not be.
Of course, I'll return it too.
That's where we introduce a factor which is the burden on the health system.
Sure, but that's why all of this is going to be together because, as Cristian
mentioned, in the end we have many lines that run in parallel. They run absolutely
in parallel because we can't.
Well, the truth is that I don't know how to continue
the talk because it was planned for something else,
but what we can do is also show you the, the, the.
What is the name of the campaign we have for the population, because it is
something
very important that we also do from the plan and also, of course, from the
veterinary
side, which I understand is what escapes us all a little, and I include myself.
In case you were interested in us telling you a little bit about this part and
continuing like this.
And of course, then leave it open for debate until you want it to be.
I feel a bit bad for all the kids.
We present the latest case.
Okay, then, the last case.
As you have seen, we work from a perspective or angle that includes
Veterinary Medicine, Environment, Public Health, and Medicine,
and we want to present this case where we know that the meat contains antibiotics.
The meat we eat is full of antibiotics; in the end, we are ingesting them, and
that is why there is resistance.
How many of you here have ever heard that?
Many.
Okay. What?
That?
What percentage of plausibility do you think that has?
That statement?
It depends on where you live.
In Spain, in Spain?
Okay.
Well, as we told you about antibiotics.
Of course they are used in animals, but only when the animals
need them, when they have a bacterial infection.
Okay.
And also because they could be used a long time ago to help them grow better.
But the use of antibiotics as growth promoters has been banned in the European
Union for more than 20 years.
Therefore, antibiotics are not used in Europe to make animals grow.
But also, when we use an antibiotic to treat an animal,
all antibiotics, all medications, have what is called
a waiting period, which is a minimum time that must
elapse between when you apply the last application of
antibiotic to that animal and when you can take food from those animals.
Okay, and this includes all breeds of animals raised for consumption,
including, for example, bees.
There may also be treatments for certain infestations, and honey is taken.
Okay.
Therefore, in addition.
In addition, there are controls.
Okay, there are controls in slaughterhouses, there are controls in
the food chain.
So this isn't just about it being written on a piece of paper.
This is under control.
Therefore, the food we eat does
not have to contain antibiotics.
There would be.
If outside the European Union there is no such control and a person goes on a trip
or
all the people who go on a trip eat meat outside the European Union and then come
back to the European Union.
In the end, the controls, that is, they can also bring bacteria, their controls,
there are border controls.
And this is something else, as I told you at the beginning.
That's why, well, I didn't want to get too involved, but I do think it's
important to differentiate between them.
Using antibiotics as growth promoters is one thing.
There are countries where they can be used, and another thing is that
the waiting time doesn't have to be respected. The waiting time always
has to be respected, okay. And when food comes from other countries
there are border controls, there are inspection points where checks are done.
Obviously, it is not possible to inspect all carcasses, all honeys, all food
products
that arrive from other countries, but checks and controls are carried out at
the level of the entire European Union.
I mean.
Homes.
But not just meat.
Directly from being in a hotel or a place.
In other words, there are studies done on people who have traveled in less than
24 hours and simply by being in one country and another place you are
exposed to other resistances, and that's just to add up.
I, for example, have worked on a project in Argentina that we
called resistances, also a research project and in
Argentina, for example, regulatory, the export.
In other words, there are different rules if the meat is going to be exported
to Europe; some products cannot use growth promoters and have applicable
legislation for those products.
Okay, not everything fits in the same way.
In other words, they have to comply with certain regulations in order to export to
the European Union.
There are many researchers who have been looking at that too, and
we're going to talk about what there are actually published studies of a trip of
less than a day.
And when you return, what do you bring back from other places?
Simply because you're exposed to a different environment?
Okay.
Therefore, yes.
Now I'm going to take advantage of the fact that you all know a lot about that.
And I also see a lot of veterinarians around here because it's a
very basic thing, but why are antibiotics used as growth promoters?
So, what does it do?
In other words, animals simply have fewer infections and that's why they grow more,
because it's something I've always wondered about, but I'm never going to
ask about it.
Well, there are several reasons.
In other words, the thing is that empirically it was seen that they grew
more.
The explanations are varied because, in addition, the doses used are
worse because the growth promoters are actually being used at
therapeutic doses, which further encourages the emergence of resistance.
So let's say they might be eliminating some infections,
interacting with the immune system, and that makes
the animal grow faster, just like there are others.
In other words, let's say that among those that promote growth, there are also
other compounds that have been used that are not antibiotics.
But come on, that would be a bit of what underlies it.
And of course, they are used massively.
So let's say it's because they are used with the feed that the animals
are treated with, so this is one of the reasons.
I don't know if it's because he says that.
Like, like.
Let's just say it was seen, uh, within the complex relationship that
exists between use and resistance, which is not all as straightforward as we might
think.
Obviously, I use higher pressure, uh, resistance, but there are
many factors that are there, and one of the things that was seen is
the relationship that when it decreased, of course, since it was a
massive use, when it was withdrawn, the effects began to be noticeable
that all those profiles no longer appeared because the biggest
problem that existed was that it wasn't the antibiotics exactly,
but it was the version that was seen that way, the most
evident was Virginia Medicine, which is a clear sense.
And there we have vancomycin, and vancomycin is the last resort
antibiotic used to treat nosocomial valvular endocarditis
infections in hospitals caused by staphylococci.
But of course, the bacteria that carries it is the whole organism and there can be
transfer between one and the other.
Then, uh, that's when it became clear that there was a relationship, when it
became clear
what was happening with the corner, it became clear that it was a problem that
of course
there were people who were dying because you could no longer treat them with the
antibiotic that was reserved.
Any other questions?
Correct.
Well, that's the message.
The meat we eat is safe.
It does not contain antibiotics.
If you don't want to eat meat, that's another matter.
And above all, you should always get your information from reliable sources.
It's useful for avoiding hoaxes, because, as in all areas of life, there are a lot
of hoaxes going around.
And I think that to conclude, I found this useful and especially
helpful, in case you want to use it in one of your sessions.
But we're going for it.
I really wanted to do the performance because we were going to tell all the
kids to hold hands with so-and-so.
And why?
Because I studied in 2013.
He said that only 5% of people wash their hands properly.
The study is old, from 2013, total 5%, that is, 5% do not
wash their hands well, 33% advertise soap, 10% do not
even wash them after going to the bathroom.
In a more recent study, in 2025, with the data on the
left, 48% did not wash their hands directly, 62% knew that they had to do
it.
During it puts less, but it is more than 20 seconds and 30%.
This slipped my mind, but 30% weren't washing their hands.
After this, you will sneeze.
But anyway, if you want to use it for a future conversation, it's something like
how shocking it is to shake
someone's hand and not know if they've been to the bathroom before and now it's
your turn.
It doesn't do anything either.
The key phrases that you all already know, and
above all we wanted to show you this year's campaign.
Let's see if there's any mention of Fleming's healthcare, which has barely
been heard today.
Well, people like the campaign about Fleming, the discoverer of the first
antibiotic, and this is his face when he has to use them incorrectly because he
takes them without a prescription.
You don't finish the treatment or you
use them against pain, fever or flu.
Antibiotics are ceasing to work in people and animals due to misuse.
Using antibiotics properly means going to the Ministry of Health.
The government of Spain.
And I don't know, for younger people, to debunk
all the myths that we have and are going to talk
about today, well, this was this year's campaign
that we are going to repeat next year.
And of course, you probably haven't seen
it and you're not, but it's for a general audience.
For more.
We launched more during Antibiotic
Awareness Week 18 throughout the month of November.
But it doesn't reach everyone.
That's right.
The plan also includes a communications team.
Dale, with whom we work on all these messages, and they are the ones who help
us,
well, to reach the younger population without having to say anything
and without having to seem like we're doing anything.
Our parents were like that when we were young.
So if you need any resources, know that you can contact us because we have them.
Furthermore, we have them in a thousand languages, including Basque; we can make
them in English, Catalan, Galician, and we can distribute them without any
hassle.
Then we were going to ask them what they could do better, since it was their
responsibility.
And finally, we are all for each other.
I don't know if you have any questions that have come up for discussion, I don't
know how long we can
have another round, because there has already been a lot of discussion, eh?
Or we can leave it here for whatever reason you prefer.
Well, many.
If we also fail to raise awareness among healthcare professionals
and not just place the blame on the population, we're doing it wrong.
Everyone at some point.
So it's simply a matter of focusing on all sectors, seeing what's being done
wrong,
what's being done right, without pointing fingers, without blaming, simply with
the sole objective of improving and ensuring that everything is for the sake
of public health.
But one of the things we always talked about, and Cristina has also
come to our class, was the microworld, and that's what's being done
now for the environmental health sector, because I think it's the most important
thing.
It's very difficult in general, but environmental health is very broad, isn't
it?
What is being done now, or what are you doing?
Well, first it seems that we don't put it first, it seems not, but they
are still finishing defining what the environment is, where things
are, where to look for it, because in the end the medicines that reach
the environment, which we were also going to talk about, the point of
taking all the surplus medicines, not just antibiotics.
He continues to the point, eh.
Then they have a transformation in the environment, for example
in multidisciplinarity it is the most consumed.
It's good for the environment.
It immediately degrades into an inactive form.
So it's the most consumed.
Okay, but that's not the main problem in the environment.
So right now we're still going to be reviewing the third
document internally and externally, because the first
one was what to look for, which was an analysis.
Furthermore, it's very methodical at a chemical level,
looking at what is released in the environment, what we can
find, and therefore, what metabolites we need to look for
that can generate resistance in the bacteria of the
environment and that can therefore be transferred to wild
animals, livestock, and people in recreational waters,
because this summer we're all going to swim there,
but we have to look for everything, all of that.
So those were the emission sources, right?
The only ones searching for the source of that emission are the hospitals.
If 80% of consumption is in the community, in fact there are a lot of
studies that also look at socioeconomic levels, showing the
different neighborhoods where antibiotic consumption is higher or lower.
In the end, there are many factors out there that aren't in our report.
This is a separate study, but it is the second report and this is the third
report.
I'm not sure if that was why, uh, what to look
for, uh, this is where it came from.
And this is when I'm not sure because we haven't reviewed it yet, but
the environmental colleagues are on it, apart from that there are a
lot of initiatives now the environment and not as understood as a
hospital environment or the environment as climate change, but as the
environment, as surroundings.
It's on everyone's lips in Europe, and Spain is quite a pioneer
in the field of environmental work, which is why the colleagues
from the agency and from Paraná are working on both sides, they
are very active with everything, of course, that's all I'm going to add.
The environment was the guiding principle of the
plan that started later, it came together in 2019,
uh, and the truth is that it began as a working group
where they tried to find consensus, to understand
a little more about all this environmental problem,
they were going to look for where to look, how, how,
how the active principles of the environment
acted, that is, and it was also starting to work on
monitoring methodologies, to draw up environmental
monitoring systems by doing pilot projects.
But of course, it does not yet have a structure of six
strategic lines, such as in human medicine or animal health.
Since we have a plan.
But it is a very active group and the truth is that
it is doing some very pioneering things that are an example in Europe
and in the world.
We've more or less closed the book, but I just wanted to
comment that if they're still working on that environmental
document, I think they should focus very, very
heavily on wastewater treatment plants.
The wastewater treatment plants are completely obsolete;
they are using treatments from 50 years ago, and with the
new medications, nanoparticles, and antibiotics, I
am sure that resistance is one of the main causes.
Perhaps the treatment of natural waters is not being done
properly because these plants are completely obsolete.
So if you can influence them to be legally obligated to regeneration
and modernization, then I think that would be an important step forward.
Thank you.
In fact, I'm just going to complement what we've been talking about,
which of course, as the environment is such a broad thing, but one of the
things they're going to start focusing on is wastewater.
Okay, so what for?
Because obviously there has to be a consensus on what we're going to look at
and where.
So it's one of the things they're working on, to have a
monitoring system, uh, of what is being found in wastewater.
Furthermore, it's not just about the medicines we don't throw down the well.
If it's because in the end we give the medications,
urine, feces, in the end everything there, even if we
do it very lightly, but they are indeed their focus.
There are many studies, based not only on wastewater from hospital and
pharmaceutical industry treatment plants, but also on community wastewater
treatment plants.
Well, then, to the last ones, the irrepressible ones, whoever you want, eh?
We want to thank the entire organization for your attendance,
the attendees, the speakers, and thank you all, and especially,
well, the students who have already left.
That's great, because I think this microworld project has been a success.
This was supposed to be the closing and closing of this project
and it has been a complete success due to the profile of speakers
we have managed to bring thanks to your availability
and I hope we have your emails and contacts.
Uh, I want to make a little channel, we want to make a little channel.
If we have any questions about young people who want to make
contact with you at the level of institutes that want to do
more projects or that want to do external internships,
CFGS, etc., then I will try, we will try to get in touch with
the speakers and we will consider this first day closed.
Thank you all very much.