The medical arms race: overcoming microbial resistance
This is an AI transcription.
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Abigail Acton
This is CORDIScovery.
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Abigail Acton
Hello. Welcome to the special edition of CORDIScovery With me, Abigail Acton. This is the World Health Organization's antimicrobial Resistance Awareness Week. So today we're talking to three EU projects that are looking at ways of tackling this vital challenge. Antimicrobials is the term given to antibiotics, antivirals, antifungals and anti-parasitic. The antimicrobial resistance, or AMR organisms are developing and are bid to counter that with new ways of controlling them is like an arms race, one that can be weighted in our favor if we use the antimicrobials that are still effective more carefully.
00:00:49:19 - 00:01:16:04
Abigail Acton
The problem is complex, affecting human animal plant and environmental health. Antimicrobials play a critical role in farming. Resistant microorganisms can develop in our food chain, moving between animals, humans and the environment. Disturbing when you consider the World Health Organization estimates the global use of antimicrobials in the livestock sector alone will rise by 67% by 2030 to 105596 tons.
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Abigail Acton
So what can be done to control the use of antimicrobials in livestock farming? And when it comes to plants, are there alternatives to the pesticides used today? While new solutions are being found? Can we boost the way our current antibiotics work by making bacteria more vulnerable? Our three guests whose work has been supported by the EU Horizon 2020 program will explore the results of their projects to help answer these pressing questions.
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Abigail Acton
These three a warm hello to Ana Bejarano who is the principal researcher on the RhizoTalk Project. Ana is a post-doctoral researcher at the University of Trento. Her research focuses on understanding and exploiting soil, microbial interactions and developing biopesticides and bio fertilizers based on beneficial microorganisms for sustainable agriculture.
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Ana Bejarano
Hello. Hello, everybody.
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Abigail Acton
Hello, Ana. Fredrik Almqvist Frederick is professor of Organic Chemistry at Umeå University in Sweden and co-founder of QureTech Bio AB. His research is aiming to develop new solutions for infectious and neurodegenerative diseases.
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Fredrik Almqvist
Hi. Thanks. Really nice to be part of this pod.
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Abigail Acton
Excellent. Nicolas Fortané, a sociologist at the French Research Institute for Agriculture and the Environment, based at Paris Dauphine University. Nikolai is interested in health issues that connect humans and animals, such as antibiotic resistance and infectious diseases. His focus is on socio technical transitions towards sustainable agricultural systems. Welcome, Nicolas.
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Nicolas Fortané
Hello. I'm really happy to be here to talk today about this very important topic.
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Abigail Acton
And we're very happy to have you. Anna, The RhizoTalk Project looked into using microbial behavior in the soil to develop effective bacterial control agents. Can you break down this goal a little for us, please? What do you mean by bacterial bio control agents? And why are these desirable?
00:03:06:00 - 00:03:36:10
Ana Bejarano
Sure. Yeah. The aim of this project is to look for alternatives to chemical pesticides, to use more sustainable agriculture approaches to treat pests and diseases. It is well known for all of us that chemical pesticides is causing death to soil and leading to alarming outbreaks and also posing resistance to many, many pathogens are becoming resistant to such chemicals.
00:03:36:12 - 00:04:08:01
Ana Bejarano
Bacterial biocontrol agents are beneficial microrganisms that live in the soil and they interact with many other microrganisms on the plants. They represent a promising alternative to those chemicals because they produce many antimicrobial compounds and they can counteract those pathogenic microorganisms that are causing death to plants. We are not toxic. They are biodegradable and they do not pose any risk to the human health or animals.
00:04:08:04 - 00:04:21:06
Abigail Acton
I see. So obviously, that would be a better channel to explore. I think that I've heard the term bioactive metabolites. Can you explain what that means and why that's relevant? What what does that entail?
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Ana Bejarano
Yeah, well, those bacterial they those bacteria biocontrol agents, they produce many, many bioactive metabolites that can be antibiotics. It themselves, they can be fungal compounds, lytic enzymes that cause death to those pathogens and also that they interrupt the maybe the the infection of those pathogens. They, they they can invade the pathogen and minimize their growth. They don't let them grow.
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Ana Bejarano
And one of the problems with those structural biocontrol agents, while they are not widely used at the moment, let's say it's because they work very well under control conditions. But when we go to the field, they need to interact with the indigenous microbiota and they need to adapt to new environmental conditions. They come, let's say, from very nice conditions in the laboratory where they are growing the optimal conditions.
00:05:21:17 - 00:05:40:15
Ana Bejarano
But when they go to the field, we have heat, we have cold, we have wind, we have rain, we have many environmental conditions that might harm the activity of those bacterial agents and also many other microorganisms that will fight or will encourage the adaptation of those microorganisms in the soil.
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Abigail Acton
So they are challenged by the natural environment in ways that is difficult. I suppose. What are those ways difficult to assess prior to using them in the soil and in the real world? Can you identify what the challenges are likely to be for any particular strain of biocontrol agents? So, for example, if you've got a promising biocontrol agent and you think you'll use it here, you know, in advance, the challenge for that will be X, Y or Z.
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Ana Bejarano
Yes, actually, for example, they will open formulations or let's say, transport that protect them, that it can be a capsule or a liquid with many protectors. We can protect those bacteria against the environmental conditions. So also by providing particles that protect them against the the you we like the similar that we do when we go to the beach and we put some sunscreen, we can do the same treating these bacteria with kind of sun cream so we can by playing around with the ingredients of a formulation, we can protect our bacteria in a better in a better way to minimize the dying from this environmental conditions.
00:06:44:16 - 00:07:10:06
Ana Bejarano
And then also knowing which are the partners that can enhance the adaptation in the soil. So which are my microorganisms that are present in the soil that will help me to colonize the plant and protect the plant against pests or diseases we might encourage and we might enhance the use of of certain beneficial strains.
00:07:10:08 - 00:07:23:23
Abigail Acton
Right. And how do I mean, I know also that in researching this area, one of the things that I found quite interesting is this notion of a quorum, your bacteria. Can you explain what that means and tell us a little bit more about that notion?
00:07:24:04 - 00:07:47:15
Ana Bejarano
Yes, exactly. This interaction is based on reaching a quorum when bacteria are in a certain environment, a sample. And if they want to coordinate that behavior, they start to grow to reach a certain population. That's what we call a quorum. And when bacteria reach this density, they start to talk among each other the same way that humans do.
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Ana Bejarano
They have to have a language that is based on the production of chemical signals that can be detected by themselves and by other partners that are not from the same family. And they come this way, communicate and coordinate. For example, the production of anti-microbial compounds. They can coordinate motility, so they will move towards certain locations, the location of the plans, and many, many other traits that are important for biocontrol activity.
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Abigail Acton
And is this something that that rather, as you were talking about, rendering the natural environment less problematic for the particular target microorganism, is this something that you can control in any way, or is there is there some way that you can release in certain environments? You say you identify existing microorganisms that could could support the ones that you're targeting.
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Abigail Acton
Can you also work out if there's a quorum?
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Ana Bejarano
Yeah, we are working actually on that. The project was my project was aimed to understand this. If we can use those signals to modulate the behavior when introducing a microorganism in the soil. And what we did was to expose our model bacterial agent to those molecules and know which were the molecules that are modulating or, let's say, promoting the biocontrol activity and which ones were the ones that were blocking the biocontrol activity of our model strain.
00:09:15:12 - 00:09:49:23
Ana Bejarano
And then the next step was to select partners that can produce those beneficial signals in order to create a consortium and not only apply in one bacteria at a time, but a group of bacteria so that our model bacteria is already encouraged by neighboring or partners in a formulation. And actually working or having a focus on the quorum is something that is also very studied at the level of human health because bacteria can communicate, but they can also cancel the communication.
00:09:50:04 - 00:10:05:10
Ana Bejarano
So there are also some partners that will quench that. It's how we call quorum quenching will silence the communication among bacteria. This is also a way, for example, for pathogens that will impede the development of the pathogen.
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Abigail Acton
And have you actually managed to work out how you could do this in the field itself? Yeah. What did you actually find?
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Ana Bejarano
Yeah, we are doing it in two ways. We are introducing these molecules in a formulation. So if we are developing, for example, a spray for spraying the plants we are introducing, we are integrating this molecule within the spray that we will apply to the plants or in another way, we are introducing microorganisms that can produce these signals. So at the time we will apply our mole that a bacterial strain on the other partner, Once they get into the soil, the partner will start to produce this molecule, so it will activate the biocontrol potential.
00:10:50:06 - 00:11:08:08
Abigail Acton
This is absolute brilliant. This is this sounds like such a great solution to to to current pesticides and quite heavy handed ways of trying to control microorganisms. Currently, as you said, it's affecting soil health. Could you tell me a little bit more about how current controls are impacting on the environment?
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Ana Bejarano
Do you mean chemical?
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Abigail Acton
I mean, when you say affecting soil health and in what way? Yeah.
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Ana Bejarano
At the moment, the major way to control pests is using chemical pesticides. Although there are also other practice nowadays, there is a trend towards using integrated pest management practices that aim to use not only chemicals but also crop rotation or understanding the weather conditions when there is going to be a pest outbreak in order to anticipate the best development.
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Ana Bejarano
And yeah, the problem of using in a massive way our chemicals is the baby means the biodiversity of the soil. So something that is being treated with many chemicals has less population of beneficial bacteria. So in a moment, let's say it seems that it's beneficial because it's counteract the pathogen if minimized the best and then they development. But in the long term it won't help because the beneficial goodness that also contributes to a stop, the pathogen development won't be there anymore.
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Abigail Acton
This sounds very much like the human microbiome.
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Ana Bejarano
Yeah, exactly. Yeah. Actually, there are some soils that are very interesting from an ecological point of view and that we are trying to imitate that they are called suppressive soils, though so is are colonized by many beneficial microorganisms. When certain pathogens arrive to the soil, they cannot develop. And it's very interesting and we are trying to understand what's happening in this kind of soils to imitate what's happening in nature.
00:12:56:13 - 00:13:00:24
Ana Bejarano
So that we can apply it to other sites that are not suppressive soils.
00:13:01:01 - 00:13:09:14
Abigail Acton
Either a particular type of plant that grows in suppressive soils. I mean, could it be that the plants that are growing in the suppressive soils are producing some sort of chemical signal that prevents the.
00:13:09:19 - 00:13:37:16
Ana Bejarano
It can be not necessarily, but yeah, of course also the plants produce molecules. They also produce some kind of communication molecules, of course, that can be not only detected by other neighboring plants, but also by all the microorganisms. They microbial community also plants communicate with bacteria and bacteria with plants and so on. And of course, the kind of plant that these in the soil will determine the microbiome of the soil.
00:13:37:18 - 00:13:45:19
Abigail Acton
And are you finding one consistent species in these what did you call them, the suppressed soils, the the soils that are naturally. Yeah, free of this.
00:13:45:21 - 00:13:52:13
Ana Bejarano
There are many sources that are called suppressive soils and they are not always a certain kind of land.
00:13:52:13 - 00:14:18:24
Abigail Acton
So that would be too easy. Wouldn't it be Hey everybody plant sunflowers everywhere and you won't have a problem anymore. Very interesting know. Thank you so much. Thanks, Frederic. You. Your project has been looking at the impact of antibiotics and how they can be used to deal with bacteria by rendering the bacteria more vulnerable to them. And of course, you're also interested in the impact therefore on the microbiome of existing antibiotics.
00:14:18:24 - 00:14:22:22
Abigail Acton
Would you have any questions for Ana considering that overlap between the work that you're both doing?
00:14:22:23 - 00:14:49:12
Fredrik Almqvist
Well, I think it's has been fantastic to listen to. And and the discussion is it's very nice in that sense that there are many approaches today, of course, which relates to what Ana has also described. So quorum sensing is extremely important in pathogenesis when you have a pathogenic bacteria. And so the question is when is a bacteria pathogenic or not?
00:14:49:12 - 00:15:20:04
Fredrik Almqvist
So and if you look at it, we talk about good and bad bacteria often in the, you know, public, but the bacteria turns bad if it ends up in the wrong place. So it can be some bacteria can be a good in one place, but then pathogenic if it ends up in the urinary tract, for instance. So controlling what the when the bacteria is going to go into certain protective states like biofilm formation is a typical situation.
00:15:20:05 - 00:15:22:05
Abigail Acton
What do we mean exactly by biofilm?
00:15:22:07 - 00:15:52:08
Fredrik Almqvist
So biofilms is an extreme problem on the planet, meaning that bacteria, they clog it together and form a very strong armory against the world. If we put it like that and of course communicate among themselves. So they do this to protect themselves from from the environment. And it can be the immune system if we're in a human. But it can also be conditions that Donna described.
00:15:52:10 - 00:16:05:20
Fredrik Almqvist
So biofilm, I mean, if you look at the hospital situation, it's typically if you get catheter ized or, you know, okay, all foreign objects, you get to imagine things.
00:16:06:00 - 00:16:06:18
Abigail Acton
Like that, Right?
00:16:06:18 - 00:16:21:02
Fredrik Almqvist
You can imagine the modern healthcare. It's it's a lot of replacements going on, right? Yeah. And if you get those infections and if they are multi-resistant, then it's a really tough case.
00:16:21:04 - 00:16:25:03
Abigail Acton
Do you have any other questions particularly directed to Anna's research that she's been doing?
00:16:25:03 - 00:17:00:04
Fredrik Almqvist
Well, it would be interesting to ask. You touched upon I mean, there are discoveries done, which is solely done because of the interplay between the bacteria and the microenvironment. They are I mean, and what you describe Anna's is really nice in the way that you need a certain community to to start to produce these active metabolites. So do you think, Anna, that we will find more new and to bacterial agents by doing so?
00:17:00:06 - 00:17:27:03
Fredrik Almqvist
There was an article in Nature a few years ago where they introduced the so-called ice ship technology so they could because some bacteria are not you can't grow them without their friends, but they they develop the technique to do so and also discovered new molecules that no one had seen before, natural products that that are now promising new antibiotics.
00:17:27:05 - 00:17:31:01
Fredrik Almqvist
Do you see more of this coming from from your work?
00:17:31:03 - 00:18:03:23
Ana Bejarano
Yeah, I'm sure there will be many active compounds that will come and that we don't know that actually only in soil. There are like 1% of the bacteria on the frontier that are known. The rest are not not discovered yet. Or as you said, they are not cold to bowel. So this is something of a problem. We know what who is there, but we cannot get it into the laboratory, cultivated and isolate these new antimicrobial compounds.
00:18:04:00 - 00:18:29:00
Ana Bejarano
There is a trend now to develop synthetic communities, So looking at metagenomics, knowing who is there and with new molecular tools and using what we can say, parts of soil is directly not culturing the soil, but introducing some soil to another soil in order to recreate it.
00:18:29:03 - 00:18:36:10
Abigail Acton
So when you say synthetic communities, what do you mean by that then I guess is communities that are developed in a way that's highly manipulated.
00:18:36:12 - 00:19:12:07
Ana Bejarano
Yes. That we know we are the representative of a certain community in the soil and we a collection of isolates. We try to imitate this community. So developing consortium based on, for example, 100, 300 different isolates, that of course, it's a very simple way to imitate what is happening in nature, because nature is there, the quantity of isolates is much higher.
00:19:12:09 - 00:19:21:03
Ana Bejarano
But these way, once they arrive to the soil, they might enhance the population off of their natural communities.
00:19:21:03 - 00:19:25:11
Abigail Acton
And isolates means because you've used the term several times the summary.
00:19:25:13 - 00:19:29:18
Ana Bejarano
Yeah. Different bacterial strains or or fund.
00:19:29:20 - 00:19:51:06
Abigail Acton
Right. Okay, that's great. Thank you. So, Frederick, to just ask you again a little bit more specifically about your project now. QTB4AMR is approaching the issue from a different angle. So you're looking at the efficacy of current generation antibiotics and how to make bacteria more vulnerable to them. First off, big question, of course, what does QTB4AMR stand for, please?
00:19:51:06 - 00:20:17:01
Fredrik Almqvist
Right. QTB4AMR is a shortening of QureTechBio that this the company we founded a few years ago and a couple of professors coming together realizing that we are doing research that can have an impact and help people in the in the future. So we we found that this company to be able to translate discoveries and for stands for four.
00:20:17:06 - 00:20:17:17
Abigail Acton
Of course.
00:20:17:17 - 00:20:20:10
Fredrik Almqvist
And then AMR is antimicrobial resistance.
00:20:20:10 - 00:20:34:24
Abigail Acton
Right. Okay. We've cleared that one up. Thank you very much. So I mean, a question that that that I would be thinking is, you know, why is it not better to actually look for new antibiotics to which bacteria are not resistant? Why isn't pharma doing that?
00:20:35:01 - 00:21:09:04
Fredrik Almqvist
Well well, yeah. So so to be clear, it's it's definitely the approach that has been taken the most the past year is to try to find a new antibiotic with a new mode of action that this and it should continue. I mean, it's really important that we find new antibiotics with new mode of actions. But on top of that, it's also clear that that we have antibiotics that have been developed and that we would like to use as long as they are efficient.
00:21:09:04 - 00:21:36:01
Fredrik Almqvist
And there are ways to to make antibiotic things more efficient. Again, there are so many things bacteria can do to be resistant. And if you then can come in with something that can make them vulnerable again, that would be fantastic. And there are, you know, historical cases. But to my surprise, it's not developed that far and not the really looked upon that thoroughly, I would say.
00:21:36:05 - 00:21:55:02
Abigail Acton
So could you give me some examples of how how bacteria can be rendered more vulnerable? I mean, I find the I find the relationship between the the resistant to microbes and the antimicrobial battle to try and control them. Fascinating how you know that the relationship it's a bit like an arms race. Tell me how you can undermine the bacteria to make them more vulnerable.
00:21:55:03 - 00:22:22:02
Fredrik Almqvist
Exactly. So there are many mechanisms that antibiotics use and how they work and a common target for many antibiotics is the cell wall, because that this does that is the bacterial difference between a chaotic human cells and and and bacteria. And but then there are I mean bacteria can have they have different set up in terms of membranes.
00:22:22:04 - 00:22:50:13
Fredrik Almqvist
Some are called gram positives and some are called gram negatives. And the difference is how many membranes they have if they have an outer membrane or not. And you have MC bacteria, which is the chief of all pathogens causing tuberculosis, a third of the world population is infected with tuberculosis. So it's an ongoing pandemic. And with this said, it's of course many things they can start to develop to be resistant.
00:22:50:13 - 00:23:16:14
Fredrik Almqvist
It can be a simple one can be that they create or they have a pump that can efflux pump out the antibiotic. That is one thing. They can also develop have enzymes that break down the compound, which is typically what happens for beta lactam, the penicillins you have so called beta lactamase enzymes that just chew up the the penicillin.
00:23:16:16 - 00:23:30:00
Fredrik Almqvist
So so those are two examples, but there are many other things that you can do and probably many things we don't know about that that will affect the antibiotics mode of action.
00:23:30:00 - 00:23:38:17
Abigail Acton
So so what do you what, what do you do to the bacteria to cause them to not be able to function to protect themselves because that's what you're aiming to do, I think.
00:23:38:19 - 00:24:06:06
Fredrik Almqvist
Right. And depending on the niche, we can also consider, yes, disarming the bacteria and not killing it. And thus would be even more even better from a pressure of developing resistance. I can take a short case. If you have a urinary tract infection, for instance, the bacteria need to withstand shear forces because pee And so they need to to establish a colony in the urinary tract.
00:24:06:06 - 00:24:33:12
Fredrik Almqvist
And then they they create the most amazing fibers called Pili. And they are made like a helical structure so they can be like a string and withstand the sheer force. It's absolutely fantastic. And they need this Pili to to hang on and start the infection and but they are not needed elsewhere. So this is typically what we would call a virulence factor.
00:24:33:12 - 00:25:04:23
Fredrik Almqvist
They need it to cause disease. So if you then specifically can disarm, remove the function of this PILI, you have an antiviral compound. And, and for some niches anti-violence would be fantastic because you especially for these diseases where you don't die the other day and then we need antibiotics for those cases. I mean, when you have a severe sepsis coming in, you don't need to do well.
00:25:04:23 - 00:25:12:18
Fredrik Almqvist
You don't have time to even know what bacteria are suffering from. So. So then the antibiotics are super essential.
00:25:12:18 - 00:25:29:01
Abigail Acton
Yeah. And I guess also what she was saying about the Pili and the way that they provide an anchor or a way for these bacteria to hold on under the pressure of moving liquid, I guess those pili that you're targeting would not be necessary to bacteria that that we would say friendly. As you said, it's not exactly the right term.
00:25:29:01 - 00:25:47:02
Abigail Acton
But anyway, living in the microbiome, because obviously you want to be able to target elements of the hostile bacteria or the problematic bacteria while leaving the friendly, in inverted commas, bacteria intact. So that would be an example where you undermine the pili, and that doesn't then affect the microbiome in the gut.
00:25:47:04 - 00:26:11:24
Fredrik Almqvist
No, exactly. Okay. In another example we we are working on is for tuberculosis. They transit into a very tolerant state. So when they are attacked by you, get them, it's airborne, so you get them into the lungs and then the immune system attacks and form sort of inclusions. They are called granuloma. And in these granulomas there is a war going on.
00:26:11:24 - 00:26:31:09
Fredrik Almqvist
So page is lowered and it's an attack on the bacteria. But they they survive this immune response and instead start to transit into a very tolerant state. So they change their yeah, they don't divide that much, but they change their appearance, if I put it like that.
00:26:31:11 - 00:26:35:02
Abigail Acton
roughly. And how can we target that? How can we. Yeah. Yeah.
00:26:35:02 - 00:27:00:09
Fredrik Almqvist
So that we, Christina Stallings grew up in Saint Louis, developed an assay to to look at this transition, because they're also in this transition. They form this biofilm we talked about earlier and we re screened compounds that could interfere with this biofilm formation. And then so it was just looking at that phenomena rather than a specific target.
00:27:00:11 - 00:27:31:06
Fredrik Almqvist
And these compounds turned out to be amazing. And we have now been able to sensitize tuberculosis in, in the lab, not farther than that. But still, it's it's really it was one of these moments when when you Wow. So these these bacteria, they get susceptible even if they are resistant to the frontline antibiotic isoniazid. If you take a resistant bacteria that is resistant to isoniazid and combine it with this compound we develop, they are susceptible again.
00:27:31:06 - 00:27:37:20
Fredrik Almqvist
So it's it's really fantastic to look in the lab at least, and hopefully it can be translated to something.
00:27:37:20 - 00:27:56:24
Abigail Acton
Yeah, yeah, yeah. It must feel like a real breakthrough. And then it makes you wonder what other breakthroughs can also be achieved, right? Yes. These kind of vulnerabilities must be fascinating to explore. I suppose it comes down to establishing exactly how the antibiotics work, Phys.org reports. The work being done by Professor Simon Foster from the University of Sheffield School of Bio Sciences.
00:27:57:01 - 00:28:20:08
Abigail Acton
His team focused on MRSA and found that antibiotics caused small holes that span the cell walls and that these holes got bigger as part of a growth associated process, eventually killing the bacteria itself. They also identified some of the enzymes that are involved in making the holes. Is this the type of vulnerability you're interested in exploiting, for example, harnessing such enzymes to undermine bacteria?
00:28:20:10 - 00:28:46:02
Fredrik Almqvist
I mean, factor this is one of these examples that the new basic science is so important to discover. I mean, well, all vulnerabilities, if they can be boosted by something, I mean, is it the way to to affect the regulation of these enzymes, for instance, or other ways? So to do that, you need to have a really strong basic knowledge.
00:28:46:03 - 00:28:48:19
Fredrik Almqvist
That's why basic science is so important.
00:28:49:00 - 00:28:49:12
Abigail Acton
And I believe.
00:28:49:14 - 00:28:53:00
Fredrik Almqvist
I hope the public will appreciate that because.
00:28:53:02 - 00:29:12:14
Abigail Acton
The basic science is very important to understand how the world works around us. Absolutely. And Q TB, For me, I believe that you are creating a method of bringing together chemical know how to harness these vulnerabilities. Can you tell me a little bit more about this so-called platform that you've developed?
00:29:12:16 - 00:29:46:15
Fredrik Almqvist
Right. It's it's fairly simple. It's when you want to change molecules and make look at different properties, you need to have a have the ability to fine tune and synthesize them in different ways, right. To change their properties. And to be honest, it takes quite a while to get those methods in place. So if you yes, find the molecule like we do, many of the antibiotics have been discovered from nature, for instance, then it's very hard to start to change and fine tune their properties.
00:29:46:17 - 00:30:10:03
Fredrik Almqvist
So we base our chemistry on more than 20 years of experience of making a certain type of a molecules and that this kind of a platform that we can quickly when we do libraries and screen, we can quickly fine tune their properties well quickly. So all right.
00:30:10:05 - 00:30:24:12
Fredrik Almqvist
So that is the way to explain it that we have a well-established chemistry in the back, meaning that we can perhaps faster than otherwise push projects further and make them useful.
00:30:24:12 - 00:30:39:10
Abigail Acton
I see. So it's a little bit like a kind of an array of methods and that you can lay your hand on the right method for the right context. More quickly because of the way that these are organized. Is that a very it's.
00:30:39:10 - 00:30:40:08
Fredrik Almqvist
A good way to see it.
00:30:40:08 - 00:30:41:02
Abigail Acton
A library, a.
00:30:41:02 - 00:31:05:19
Fredrik Almqvist
Molecule can be seen as a you have kind of a center of the molecule and then you decorate it if you're in a simple way. And then what you decorate is actually creating the final product, right? So if you want to put something in the in the corner of the molecule and something in the right corner and you know, so it's yeah, it's really fascinating, to be honest.
00:31:05:19 - 00:31:11:12
Fredrik Almqvist
I mean, that's why I got hooked and that's why I sound absolutely. That's why I am a nerd in organics. And yeah.
00:31:11:15 - 00:31:25:04
Abigail Acton
So I could, I could totally see why whether, whether tweaking this bit over there will have this reaction. And if you do, will that happen? Yeah, absolutely. Does anyone have any questions here for Frederick and and maybe you do given your overlap between the the two concepts you're working on.
00:31:25:06 - 00:31:41:21
Ana Bejarano
This is very interesting what you're working on. How do you explore this, this resistance? How how do you really understand how you can make more resistant to antibiotics such an organism.
00:31:41:22 - 00:31:45:05
Abigail Acton
More vulnerable to antibiotics? Yes, be obvious.
00:31:45:07 - 00:31:50:01
Fredrik Almqvist
But well, you have a point. You can also make them more resistant so that that is true.
00:31:50:01 - 00:31:51:09
Ana Bejarano
Sorry, sorry
00:31:51:11 - 00:32:20:14
Fredrik Almqvist
Now. But there are different ways to explore for, first of all, what your compound does alone. So if you have a standalone situation, how will the bacteria respond? And if you know that the compound is creating a certain phenotype, meaning that the bacteria will will have a certain set up, you can look for that and see if if the bacteria get more, you know, used to the compound and can withstand the compound over time.
00:32:20:14 - 00:32:51:09
Fredrik Almqvist
So you, you, you take it in several rounds and see if resistance appears. But for these cases when we have a non antibiotic compound just disarming, we have done that the couple of times like for for bacteria that that you may may look at in the soil listeria listeria is a typical problematic bacteria that lives in the soil but can be translated into the food chain.
00:32:51:09 - 00:33:11:04
Fredrik Almqvist
Right. And we have compounds that can take away their ability to infect if they come into the humans and or animals. But this compound have no effect on their living in the soil. You know, having fun in the soil doesn't is not the problem with these compounds.
00:33:11:08 - 00:33:20:12
Abigail Acton
It's just it's fascinating the ability to to to fine tune so well and to target so well, you know, affect it in this context, but not in that context.
00:33:20:12 - 00:33:56:11
Fredrik Almqvist
So that is the future. It's like the precise, precise medicine. But I need to stress that it works in certain niches and in infection is very, very I mean, if we take chlamydia, it's typically a situation where disarming would be fantastic because you don't die from a chlamydia infection, at least not quickly. And and it would be easy to diagnose, but today it's treated with normal antibiotics and more than 140 million people on the planet yearly yet treatment for chlamydia.
00:33:56:13 - 00:34:32:01
Fredrik Almqvist
So and of course that antibiotic should be used for this case is when you have sepsis and die within in a day or two. So you have to find these knee issues when it still make a huge impact on the planet. If we can find solutions for those bacteria as well. And the focus is that it's easily it easily gets only on this, you know, killer bugs and situations when we we also need to do research on other bacteria because we need treatments.
00:34:32:03 - 00:34:32:21
Abigail Acton
Ana.
00:34:32:23 - 00:34:57:15
Ana Bejarano
Could the maybe molecular tools also work for for this bacteria that you talk about neglected and tuberculosis like nowadays there is great focused on CRISPR on such kind of tools have you ever thought of of using those with such a complex microorganism.
00:34:57:17 - 00:35:25:10
Fredrik Almqvist
Well it's it's to be honest, not within my expertise since I'm a synthetic organic chemist. But I can definitely see your point that I think it will open up many doors, especially more related to your field. If you can introduce a bacteria in the that out compete make the bacterium or so that would be. But I don't know it's it's a bit farfetched to me and.
00:35:25:12 - 00:35:27:10
Abigail Acton
Not not exactly your field.
00:35:27:12 - 00:35:35:20
Fredrik Almqvist
Although although a manual did her discovers here in the room and I know her so it's that you know the research.
00:35:35:22 - 00:35:37:00
Abigail Acton
Looking at this yeah.
00:35:37:06 - 00:35:43:08
Fredrik Almqvist
It was developed in email so it we have celebrated a lot her Nobel Prize I can tell you.
00:35:43:10 - 00:36:02:08
Abigail Acton
fantastic. Nicola your project roadmap wanted to foster transitions or still does want to foster transitions towards a more prudent anti-microbial use in animal production. Can you tell us a little about the current situation? We frequently hear that there's an overuse of drugs such as antibiotics in farming, but what is the extent of the problem?
00:36:02:10 - 00:36:26:14
Nicolas Fortané
Well, as you know, antimicrobial resistance is a is quite a big issue, something that we call usually like global health. And one issue because actually, of course, the overuse of drugs in the in farming and especially antimicrobial research is one part of the. But there are many causes and many consequences to that. And of course, overuse is also happening in in the in human medicine.
00:36:26:14 - 00:37:01:13
Nicolas Fortané
For example, what we can say a guess about the use of antimicrobials in the in livestock farming is that it's also quite diverse in certain region of the world, in particular in Europe, reduction of antimicrobial use is under way, but it's also a bit more complex than that because we need to understand better what is good. You see where exactly it is that you're seeing and what would have a greater impact because of course we can use antimicrobials for prevention proposed for therapeutic proposed in other region of the world for growth promotion purposes.
00:37:01:19 - 00:37:23:10
Nicolas Fortané
And none of that doesn't doesn't have the same impact necessarily on make of your resistance. And so we need to be aware that worldwide it is expected that the use of antimicrobials in livestock farming is going to go over over the next year, over the next decade, because the demand, especially in meat, is rising.
00:37:23:15 - 00:37:48:22
Abigail Acton
Yes, I understand that. The World Health Organization estimates that the use in livestock sector alone will rise by 67% by 2030. Yeah, quite phenomenal, really. So why I mean, road map was setting out, I think, to change perceptions and to identify historic reasons and and and to use that information to to change perceptions currently. So why is this such an area where there is so much dependance?
00:37:48:22 - 00:37:53:17
Abigail Acton
That's a big question. But, you know, if you could sum up some reasons for how this has come about as a problem.
00:37:53:19 - 00:38:16:11
Nicolas Fortané
Yeah, I mean, there is as a data, there is a very long story here. And what I'd like to stress first is that you used a very interesting word like you talked about dependance and that we're talking here about the systemic dependance. This is our food systems and our health systems that that are structured in a way that they rely so much out there.
00:38:16:11 - 00:38:47:05
Nicolas Fortané
How rely that so much on the use of antimicrobials? And there is a an English anthropologist called the center who speaks about antibiotic as as a quick fix as a way to easily fix our need in productivity profitability and things like that to gardening, the way we produce food, the way we heal and cure people. It's antibiotic, as she said, our infrastructure, our social infrastructure.
00:38:47:07 - 00:39:20:17
Nicolas Fortané
And this is why I mean, this dependance that you mentioned, I really consider it is a systemic one. And of course there are perception, behavioral aspects of the of the overuse of antibiotics, because I'm not saying that it is not something that we can or should target and that we could work on, but it could never work if we also if we don't address all the structural factors in terms of what our farming systems or how the vitamin like market works, what is the structure of the food chain?
00:39:20:23 - 00:39:34:10
Nicolas Fortané
How is the demand regarding meat and other products? And if we if we don't try to work on all of that and basically we won't reduce our systemic dependance on antimicrobials.
00:39:34:12 - 00:39:44:22
Abigail Acton
And what is roadmaps role in trying to work on all of that, because I know that the project is multi-pronged. You are trying to address different angles, different levels. Tell me a little bit about the work of your project.
00:39:44:23 - 00:40:21:10
Nicolas Fortané
Yeah, of course. The roadmap is trying to encompass this, these various aspect, these various issues. I mean, first of all, we have a series of tasks trying to understand the various factors that are that have at least, you know, developed this this is massive use of anti-microbial and then both structural and behavioral factors. So as I said, structural food, because as a practice of the stakeholder, the crucial role aspect of knowledge and we are implementing quantitative and qualitative surveys to to better understand.
00:40:21:12 - 00:40:24:14
Abigail Acton
Who's participating in the service. Who are you asking?
00:40:24:16 - 00:40:34:04
Nicolas Fortané
we we are 17 partners in about ten countries in Europe, and we are, you know, undertaking surveys in ten countries.
00:40:34:04 - 00:40:38:02
Abigail Acton
But is it farmers or is it vats or is it farmers and vats or.
00:40:38:04 - 00:41:03:15
Nicolas Fortané
So on the on this farm level aspect? Yes, it's farmers and vets and some livestock technicians, but we also have surveys and trying to understand the the the strategies of some individual stakeholders because what they do matters is where so the pharmaceutical company, the agrifood companies. And we are also trying to assess the impact of some national action plans.
00:41:03:17 - 00:41:11:18
Abigail Acton
And what are you finding? What's coming through? I mean, maybe it's early days, but do you have some overall kind of image, you know, ideas coming through?
00:41:11:20 - 00:41:19:06
Nicolas Fortané
Yeah, sure. I mean, the project is still we are midway through the projects. We don't have the final results short term.
00:41:19:08 - 00:41:21:09
Abigail Acton
And any trends emerging then.
00:41:21:11 - 00:41:51:24
Nicolas Fortané
Yeah, first of all, I think this awareness that everyone is calling upon about the problem is here. Like of course this is sometimes it's a bit diverse, but that's farmers. Also the industry is aware of, of the antimicrobial resistance issue, and especially in Europe, we are already in the trends of, of addiction antimicrobial use. But of course there are policy societies, policy cultures that diverse in the north of Europe, the South of Europe, the west of Europe.
00:41:51:24 - 00:42:34:02
Nicolas Fortané
So we don't bring up the same solution, the same way of implementing the solution. And of course, the impact could be a slightly different depending on the countries. What we also see is, is a development of quality labels by the food industry that is trying to reduce antimicrobial use, but that has also and which does actually reduce some of your news which contributes to this collection, which which also has other effects or impacts on the structure of the food chain or on the food market in terms especially of a concentration of the chain industrialization or intensification of the practices.
00:42:34:04 - 00:43:03:24
Nicolas Fortané
So it is still a challenge how the reduction of anti-microbial use will contribute or not to avoid political transition. And for me, as a sociologist, I will always try to keep in mind and to communicate on the fact that of course using anti-microbial use is an objective that we must achieve. But maybe it is not the only or the final objective, because the objective is this transition towards a more sustainable way of producing our food.
00:43:04:01 - 00:43:14:23
Nicolas Fortané
And and we we need to find solutions to reduce antimicrobials that also have an impact on on this transition towards sustainable agriculture.
00:43:15:00 - 00:43:41:01
Abigail Acton
It's interesting that you're talking about sustainable agriculture, because actually that brings us back to the work that Anna's been doing and in the rise of her talk project because she's been looking at sustainable alternatives to to the current use of pesticides by using microorganisms and the way they into communicate and interact as natural ways of of reducing the number of problematic microorganisms in the soil.
00:43:41:03 - 00:43:44:03
Abigail Acton
Anna, would you have any questions for Nicholas?
00:43:44:05 - 00:44:17:15
Ana Bejarano
Yeah, actually, if I'm not mistaken, I think there are some trends now to use water derived from farming, for example, from fish farming to be used in agriculture as a way to stimulate crops. So by stimulants because of all the manure on and so on. And I my word of my heard or read that actually the use of antimicrobial compounds is a bit of a problem.
00:44:17:15 - 00:44:46:20
Ana Bejarano
If there are some residual amounts of both in these waste products because then they will come to the crops, they will spread all around and then, you know, if there are any kind of three plants in order to silence these antimicrobial compounds in the waste, or how can we get rid of them in order to use circular...
00:44:46:24 - 00:45:20:19
Nicolas Fortané
That's a very interesting question. And unfortunately you are probably asking this question to the right person because, you know, I'm not a biologist and I'm perfectly aware of all the technical aspects of of how basically we can remove these compounds from from the waste and stuff like that. But, but it is definitely I know that not in the roadmap, but in other projects like working on developing alternatives as well to antimicrobials or trying to develop techniques or technologies that are trying to prevent the spread of resistance genes in the environment.
00:45:20:19 - 00:45:51:07
Nicolas Fortané
Because especially AMR in the environment is is basically for me, I think it is a new topic, the new issue that something that we have missed for decades and that relatively it is relatively new. I mean, probably in the last ten years. But we have focused so much on the, you know, the the the spread and the dissemination of the genes between humans and animals and forgetting like the third pillar of the one health concept, which is the environment and the ecosystems.
00:45:51:09 - 00:46:05:20
Nicolas Fortané
And and they embrace such impressive, you know, topic that we must address in such a way. And I think we are just starting to do it. So the question is very relevant to my opinion.
00:46:05:22 - 00:46:29:20
Abigail Acton
Excellent. Well, thank you very much indeed. And thanks to all of you actually for this very interesting debate, very topical, given the fact that it's the world Health Organization's week of antimicrobial awareness, raising, the work that you're all doing is obviously very important, and I wish you good luck going forward with all of it. Thank you very much for participating today and for giving us your time.
00:46:29:22 - 00:46:34:11
Ana Bejarano
Thank you. It was very nice to participate in such a podcast.
00:46:34:12 - 00:46:35:00
Abigail Acton
Excellent.
00:46:35:03 - 00:46:36:18
Ana Bejarano
Very interesting to meet you all.
00:46:36:19 - 00:46:37:13
Abigail Acton
Thank you, Anna.
00:46:37:17 - 00:47:06:09
Fredrik Almqvist
It has been a pleasure. I mean, this discussion is super important and it's really fantastic to see how different disciplines contribute to this very important task. And we haven't really touched upon it. But climate change that we all discuss is, of course, also impacting this situation. And I know you touch upon it and it's it's for sure also interconnected with antimicrobial resistance.
00:47:06:09 - 00:47:09:07
Abigail Acton
So as it's interconnected with absolutely everything.
00:47:09:09 - 00:47:10:18
Fredrik Almqvist
A lot to look forward to.
00:47:10:20 - 00:47:12:22
Abigail Acton
Yes, indeed.
00:47:12:24 - 00:47:23:13
Nicolas Fortané
Yeah. Thank you very much as well. And I'm very happy to have contributed to the to this podcast. And I think it's very important that we can talk about this such a such an important issue.
00:47:23:19 - 00:47:31:02
Abigail Acton
Well, maybe we'll have another one next time. The World Health Organization has another awareness raising week. Thank you, Nicholas, for joining us. Thank you, all of you.
00:47:31:02 - 00:47:32:11
Ana Bejarano
Thank you very much very much.
00:47:32:11 - 00:47:33:14
Fredrik Almqvist
Super Bye bye.
00:47:33:14 - 00:47:34:04
Abigail Acton
Bye bye bye.
00:47:34:07 - 00:47:34:23
Ana Bejarano
Bye.
00:47:36:18 - 00:47:53:08
Abigail Acton
are you interested in what other EU funded projects are doing to tackle AMR? The Cordis website will give you an insight into the results of projects funded by the Raizen 2020 program that are working in this area. The website has articles and interviews that explore the results of research being conducted in a very broad range of domains.
00:47:53:14 - 00:48:13:07
Abigail Acton
Whether you're interested in corvids or covered, there's something there for you. Maybe you're involved in a project or would like to apply for funding. Take a look at what others are doing in your domain, so come and check out the research that's revealing what makes our world tick. We're always happy to hear from you. Drop us a line editorial at Cordis dot Europa dot EU.
00:48:13:09 - 00:48:20:05
Abigail Acton
Until next time.
Antimicrobial resistance (AMR) is a complex problem affecting human, animal, plant and environmental health. Antimicrobials play a critical role in farming: resistant microorganisms can develop in our food chain, moving between animals, humans and environments. Disturbing when you consider the World Health Organization (WHO) estimates global use of antimicrobials in the livestock sector alone will rise by 67 % by 2030 to 105 596 tons. The imperative to make people aware of the dangers of the misuse of antibiotics, and other antimicrobials, is behind the WHO’s annual World Antimicrobial Awareness Week. This special episode of CORDIScovery, timed to coincide with the Week, invites three guests to share the work they are doing to win the race between the resistance microbes develop, and the ways we have to control them. How do you target the bacteria you want to kill off without wreaking havoc on the colonies of ‘good’ bacteria that are so vital to our well-being? And if a bacterium has evolved to work around the impact of an antibiotic, can we tweak the chemistry between them to render the bacterium vulnerable again? Fredrik Almqvist, co-founder of QureTech Bio AB, explains the work the QTB4AMR project is doing to change the chemical relationship between an antibiotic and its target bacteria. The weird and wonderful world of soil microbes, their relation to the plant roots around them and the ways in which they communicate, could give rise to a new generation of biopesticides. Ana Bejarano explains how her RhizoTalk project is looking for ways to increase that possibility. How did farming become so systemically dependent on antibiotics and is it too late to turn that around? Nicolas Fortané, who coordinates the ROADMAP project, takes a look at the problem from a social science perspective. ‘Spread awareness, stop resistance’ is the title the WHO has given to this year’s World Antimicrobial Awareness Week. Hear what our guests are doing to do just that!
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If you have any feedback, we’re always happy to hear from you! Send us any comments, questions or suggestions to the usual email address, editorial@cordis.europa.eu.
Keywords
CORDIScovery, CORDIS, QTB4AMR, RhizoTalk, ROADMAP, antimicrobial resistance, farming, World Health Organization, bacteria, pesticides