What is antibiotic resistance? - podcast episode cover

What is antibiotic resistance?

Oct 31, 202434 minEp. 96
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Episode description

And how are researchers tackling it? Antonia, Emma and Ellie discuss how we got here and what might be done in the future to counteract these drug resistant bacterial strains. Plus we take a sneak peak into the life of PhD student Emma and explore how computational simulations could be helping develop the antibiotics of the future.

Transcript

[Music]

hello and welcome to technically speaking where scientists and Engineers come together to chat about common interest share knowledge and satisfy some curiosity I'm Antonia and I'm joined by Emma and Ellie to talk about antibiotic resistance what it is and what is being done to address it so to start off with I thought it might be a good chance to learn from Emma because I think you've done some research in the area of antibiotics resistance I actually I actually have

and I I I think I only realized when we were planning this episode how much stuff have actually done of antibiotics but um yeah so my masters was essentially looking for like alternatives to antibiotics I did a lot of research into how they work and what's wrong with them and did some like lab testing with antibiotics and computational simulations as well and now actually my PhD although it's not on antibiotic alternatives um it's very very close to that so I

still kind of a lot of the papers I read are still about Asos resistance so maybe I am some form of Resident expert at the moment which is quite interesting you've done more research than me so I'm happy to give you the expert title dice oh yeah for sure for sure so Ellie you're not a expert as you said uh in your words but you did study zoology at University and did antibiotic resistance come up there I was trying to make any link that I could think of between antibiotic resistance and

anything I studied at Uni but I can't really think of anything the best I could do is xotic diseases but I don't know enough about it to be like yes and then they developed and do it I mean I don't know is the honest answer but I'm very happy that we have Emma cuz she can teach me all um the only thing I really know about antic biotic resistance is like MRSA that's like the best I can come up with and even that I don't know that much about so hopefully we will all

learn a lot through the course of this episode yes but on the topic of MRSA um what what what is MRSA so when I actually I think you might think the same Elena when I was younger and I heard people talking about MRSA I thought it was itself like a disease yes but what it actually stands for is the sa is a strain of bacteria and the r stands for resistant so it's just resistant strains of bacteria that have been given this kind of umbrella term of MRSA um which I didn't actually know for

honestly a shocking amount of time for somebody who no today I today I learned I just assumed it was like some super bug that people get in hospitals but I didn't realize that it could be more than one disease or like different bacteria creating different diseases I'm already confused please please lead me the way the sa is um is a type of bacteria it's the a is orus and that's nice to pronounce but the S is hard to pronounce um but it's a we won't make it the Latin no it's a it's a strain so

it's um just like ecolizer strain of bacteria um this essay is also a strain but can develop um it's one of the first strains that started to develop resistance and why people had to start get a little bit worried um and so I think that's why it's become this kind of big term for bacterial resistance and antibiotic resistance so if we said someone had MRSA does that mean they have a disease or is it just they have some resistant bacteria I would say they have some

resistant bacteria but if they also have um if that if they have that bacteria that's resistant then that bacteria will have the effect of a disease like it'll be a bacterial infection because the antibiotics won't work so I guess the whole like uh labeling of disease is very it's it just depends on how you want to call it but I always think in terms of if you have the bacteria and if it's resistant I always just think of the bacteria rather than like a disease

or an illness or something but I think that's because I'm used to just doing stuff in the lab rather than actually real people I guess the bacteria is making you sick right so you have an illness regardless because you feel ropey and then what's making you sick is then uh resistant to the things that you would normally use to cure it yeah exactly see expert already it's been a whole two minutes I'm I already nailing yeah so how big a problem this is I think you shared with us an article about

the number of deaths that could be attributed to uh antibiotic resistant diseases or death um sorry no infection which led to death or was somehow a death relation to an antibiotic resistant disease oh no I've definitely messed that up no I it's all the yeah it's all the same um but yeah know so I yeah um I actually found another stat that was that if we continue with what we have currently prescribed right now with like the antibotics that we have right now and knowing how quickly bacteria can

develop resistance to them there was a bit of a scary stat that um the death toll um attributed to anti resistance related deaths um is expected to be 10 million annually by 2050 oh dear which is it seems like a very big and scary uh number and it definitely is but also I think that's what's led to a lot of like new research happening about antibiotic resistance and bacteria in general to try and understand how they work and how we can actually move on and start to

look for new things because it was kind of something that people had all these antibiotics and they worked so everyone was using them and so people didn't actually there was definitely like a a lull in antibiotic resistance groups where people are like we have this and it works and now everyone's like let's make some new things so it's a scary St but definitely um I think people are already kind of working on that now yeah and this article that you shared first um estimates about almost 5

million deaths a year are associated so that's like double in just 25 years and obviously in that time hopefully our medicine would have uh improved but um SS like yeah we need to invest more in find finding alternatives to antibiotics so what makes antibiotics not work on these uh mrsas I can I can definitely answer that one um so um one of the main reasons why bacteria can develop resistance to antibiotics is if it's quite helpful to think about it sometimes in the way that

humans evolve like the bacteria are just essentially evolving to not be affected by these things that are killing them but the reason why we see this evolution of bacteria is because they have such a short lifespan so they can kind of mutate and grow a lot quicker than human cells can so you can observe you know in the space of um you know a few hours depending on the bacteria um multiple generations and so it's essentially Darwinism so El might be a bit more of

an exp I heard Darwin and suddenly my ears put out yeah uh so I will I guess paraphrase um Darwinism but the bacteria will just develop a random mutation um and that will you know that might make them more resistant to the antibiotic because antibiotics can work in a few ways but penicillin which I would say is probably the most famous uh antibiotic works by stopping how the bacteria make their cell walls so when the bacteria try and divide they can't actually make a cell wall so the

pressure is all wrong water molecules can move in and out when they shouldn't and so it just kind of can't survive it's like a balloon with really bad skin that it just kind of Pops all the time exactly exactly um and so you could get a resistant bacteria strain that might have something else on its cell wall that means that penicillin can't Target it and so it's that's just one aspect of the bacteria that that an antibiotic is targeting but there's obviously lots of different

antibiotics that look for different things in bacteria um but you just get this resistance from essentially just Evolution yeah they just mutate so fast that they mutate ways to survive right so that's what they're trying to do so if this is targeting their cell wall then they mutate something that means it doesn't affect it anymore yeah I'm trying to remember there was this fox study I think and they were breeding generations of foxes and then they eventually exhibited more like

domesticated uh trait in a really short time span I don't know if you could elaborate but it kind of reminds me of how short bacteria mutation cycle might be even faster than that in like a sort of years like span it's supposed to like anything isn't it if you think like a human gener generation takes so long for any changes to come through but bacteria just don't work like that and even foxes like their lifespan is much shorter they can have multiple lits a year presumably so like

even those generations and then they grow up they don't they're not waiting I don't know what 15 years 13 years to be able to be sexually mature to then breed like that's why it's all so staggered in people but bacteria just can you know mutate and grow and breed new generations much much faster so I guess this is why this is so common because it's so rapid right like it takes a long time to develop drugs potentially we can't keep up with all the mutations that the bacteria are doing exactly

exactly um and we were talking about cell membranes before we went on this little tangent um and I think you did some research as a biophysicist on membranes yes I did and I would definitely identify as a biophysicist um some people call be a chemist which I don't like but yeah um yeah no exactly so um what my project was essentially on is that fundamentally human cells membranes are more or less not charged um of course it's always always gets a little bit more

complicated than that but as like a blanket human cells um not really charged but bacterial cells are negatively charged and so physicist in me and well the group came up with it before I did but was if you have these kind of positively charged proteins get attracted to the bacterial membranes um and they don't get attracted to the human cells and the idea was that was when they bind to the membrane they can stop it from dividing in the same way that essentially penic works by just

stopping it stopping a process of the replication from happening and that's essentially like the main I think um research focus of um bacteria and antibiotics um is essentially the biggest question to ask is what is the difference between human cells and bacteria cells because we do not want to Target our human cells but we do want to Target the bacteria and so there's um as you can quite a lot of differences and that's um what a lot of people are focusing their

research research on depending on these differences because that's how you get a really successful uh antibiotic how many differences do you think we're working with like on the scale of 10 hundreds thousands oh I think yeah I hope Lots I feel like that's better like the more differences we can Target surely that's more productive for making new I think it's like even I don't know thousands hundreds of thousands I think there's just there's just so many because so so many

possibilities yeah exactly exactly um and I think like a few of the like penicillin I don't think like people discovered it but it wasn't like synthesized in the lab it came from some derivative of a product that was used um I think it might it could have I'm not sure at this point but it could have been used for something else and then people tried it um on kind of a bacterial infection but that kind of uh targets one specific thing and so the bacteria have had time to develop

resistance to that and so people are trying to look a little bit more smarter smartly to think where else can we look to try and Target and so there's a lot of stuff involving um looking at how the DNA replicate as well um which is the part that's semi- related to my PhD so loads of people people are really got their thinking caps on to try and think of the different differences is it likely that some of them will become obsolete like penicillin's been around for hundreds of

years is that going to stop being effective at all in the future like is this why we have to make more because eventually we'll just be like useless as as a drug I think that I think if we continued to use it and not have others at the same rate then that is what what we would have um but I think because we are kind of aware of that and we're using other ones it's a lot more difficult for the bacteria survive when you prescribe for example a hospital where just prescribe one antibiotic

they'll prescribe a lot because they don't want to have everyone always on the same antibiotic um but I do think it's a good point I think it would happen if we were only using penicillin for everything which maybe wouldn't even work anyway but um yeah so it's the reducing using it and it will still be effective because I think there's some antibiotics which [Music] are really really really effective but very very risky to have them uh become the bacteria become resistant to them

because they're so good so I think like some hospitals only prescribe those in like really dangerous cases and I think like that's another example of I think scientists being a little bit smart is they always there's a lot of backups that are still kind of there that people can still use and so it's not like this huge Panic of what are we going to do it's it's kind of like this is just something we need to be actively thinking about for the future and yeah it's kind of nice that people are

already thinking ahead of the game I just saw um Ellie's cat go on screen and it reminded me about flea treatment um for my cat and they said if you are on a plan plan with a vet it's better because they will swap out um the treatment if they find one is becoming more prevalent and they can Target it rather than you going to the pet store and just buying whatever off the shelf cuz you won't know the sort of trend that is happening so it sounds like that's what

hospitals are doing is they're kind of going okay loads of people are getting prescribed X so we're going to make sure that that uh that infections don't become resistance to X so we're going to mix it up a bit I just always remember being told to finish my course of antibiotics like that was like really drummed into me as a child that like you couldn't possibly only take 12 out of 14 that you had to take them all otherwise the antibiotic resistant bacteria would come for me yeah

would come for you otherwise think it wouldn't be effective or something or it would make the doctors sad and I was a very people pleasing child and I would not have done that but is that is that like relevant is that just something that people tell you I think it is I think it's it comes from you want all of the bacteria to be gone because I don't know in case over the time that you don't take it they could develop something I'm not even sure to be honest

I think it is so that you don't have any like survivors that can I don't know take overing your system yeah but I think it's also like a a lot of the prescriptions that there's so much science behind when to give prescriptions to people and how if you should take it in different times a day and it actually this is maybe a bit of a Sidetrack but um it's really interesting reading drug studies where they change the dosage um at different times of the day but the overall daily dosage is the

same it just depends on when you take it has a massive effect on how um effective it is wow why a huge significant difference I don't know if it's um you know if you take it after you eat it kind of can be absorbed better or something um that's just a guess but um it's really crazy um so a lot of like drug final drug development studies is with like clinical trials with people where that people just have different um dosages and very different times that's wild maybe it's all in the timing you

never considered that maybe the bacteria go to sleep at like 3:00 in the afternoon so expect it or maybe when your own immune system is the strongest at a certain time or it's woken up that's true maybe cuz it takes me a while to get going in the morning so I feel like you know you got to hit it while we said this before about the um athletes right about the ideal time to compete with the Olympic one so maybe it's like similar that there's like a peak time of day where

you're at your Optimum and then maybe if you're on well you should take it then to like give it the best chance of working but it equally could just be like it gets absorb better if you've just eaten lunch yeah I think um there needs to be further study on that there you are Emma this is your next PhD yeah know I'll I'll work on it but it is really because I always love to find out like what um because I think i' when I've been on some antibiotics it's actually just been like once a day and I

haven't even thought to take it at the same time um but some people get told to have it after every meal and so now I'm definitely I'm asking my friends on antibiotic when they're like oh I'm on antibiotics I'm like first of all when are you taking it which anotic cuz I might have used them in the lab they might be in my freezer and I'm just curious to know um which ones people are on now that I have a few names are you keeping a log and you're going to have some kind of Messa study to come out

thing is there a lot I think I think if a few times it's happened since I've started my PhD and it's uh there's only been one that I actually have used before so um I'm still waiting you're not prescribing it straight out of the lab that sounds like is offering them willy-nilly to all of our friends that sounds like how we get antibiotic resistance Emma is the source after all this time yeah it's been me my whole M it's like it started in 2022 when [Laughter]

I it's not that much of a recent problem is it antibiotic resistance though no I think it I think it has been around for a while because I think it's it comes from the fact that people didn't envision in them not really going wrong so when people started to see this then they were like oh we should now I should do something about it um which I like totally agree with I feel like if I'm like a doctor and something's always worked I wouldn't plan for the future and be like maybe we should think of

something right now that also works because the whole drug development industry can take like 15 years and or even longer than that and like I think I think it's like 2 billion in the US to go from initial idea to approved and like produced drug so it's a huge industry and so I imagine it's a bit of a a while ago it was definitely if it ain't broke don't fix it but also it is a different job really drug development versus being a doctor or pharmacist who is

prescribing the the medicine like you'd have to take time out to figure out that kind of stuff no ex exactly there's a whole like um there's a huge Pipeline and loads of different stages of that pipeline so if I'm working in drug Discovery now I'm kind of just looking at the start of it which is where you just test loads of different things see what works try and understand why and then from that work to how can we make this better but then all of the like clinical trials

and human trials and stuff that I don't do in my PhD I mean I guess it's just like three or four years so I wouldn't even be able to throw out my whole time if I worked on it completely get from start to finish which is yeah interesting that's so interesting so should we be worried then because they're clearly mutating very rapidly and as you just said the drug you know pipeline takes a long time so like is this going to take over are they going to you know

outpace medicine what medicine can do in the time limit and phds and researches and everything or am I just uh paranoid I think it's a I think it's a valid concern because I think but I also think whenever I read stuff about Healthcare it always is written in a way that is a little bit scary um but especially what I think is really important recently and it relates a bit to some of the work that I've done is a lot of people now um are using computations and simulations and

especially AI to kind of shorten that first stage of the drug development process so it's not like as simple as chat gbt can you make me a an antibiotic that isn't going to be um that would be so resistant but um to use tools like that to really like when you just have to test loads of different things instead of synthesizing those individually which could be like 2,000 to 5,000 molecules and even then that's quite that's quite small already sometimes you have like two million

possible compounds you could do which is impossible to synthesize those and test those in the lab like that would just take ages and that's what people kind of used to do was test all these compounds but if you use um different kind of computational simulations to make compound is just kind of a few clicks of a button and then to test it depends on what you're doing but you know you can test thousands in a day and that will give you this kind of ranking that maybe

isn't perfect but it's something to start off with and then you take those top compounds and you can invest your efforts into testing those better so I think with the kind of new and it is very relatively new I think molecular Dynamics computational simulations started in around you know 2010s 2015 that is massively changing the drug Discovery industry and I think it's actually really exciting um to see where that's going and um yeah know I think it's definitely definitely I wouldn't be

worried about it because the computational people are on it and also the lab people as well that's reassuring I'm glad that you're you know you're in the no you've got a system I don't know anything about computational simulations or AI but I feel glad that you do and that you're using it for good a force of good in the world against antibiotic resistance so with the simulations is it that you would narrow down things and then someone would actually sympath S I can't

speak today so with the computational simulations would you look at everything and then narrow down some for someone to then actually sympathize in a lab and then move on to the next development process so it's like adding an additional Step at the front yeah ex I mean that's exactly the stuff that I'm looking at I mean I do both experiments and simulations so the idea is that I will then test them myself um and but a lot of people are working on uh can we narrow it down to

you know very very few molecules and then we do the lab work and then it's kind of saves everyone time and what a really important thing about the simulations as well is it's not just that it makes it quicker but also you can actually see the different atoms interacting and they're really accurate they're based on like um they're trained on like experimental studies so you can actually see where the um antibiotic is interacting with on the bacteria and then you can even mutate the bacteria

yourself in the simulation and see will it survive this mutation genuinely cool and then you can see how kind of robust your antibiotic is going to be by running these simulations because in the lab you don't get information such as oh where exactly does it interact with the bacteria but in the simulations you can physically see it kind of moving in and sticking to the area that you wanted to and so it's really cool and really helps people understand actually what's happening with these

drugs that's so clever I don't know anything about computer simulations but I'm imagining like manipulating all the tiny parts of it to like see what happen if you increase this bit or decrease this bit or make it positively charged or anything like that and then yeah I can see how then you could like future proof it as well in theory I mean obviously it takes maybe slightly more time to go from that simulation to like what it would be like in practice maybe there's

probably some disconnect there but still like it's shaving off hours and hours of work and it it also sorry exactly I know I was just going to say exactly and it it sounds like you might learn something that you didn't know about how bacteria behave cuz you've kind of got the rules of physics and biology that you understand and then apply it to hopefully get the same result in real life um and learn what actually was beneficial about using that particular molecule against that particular

bacteria exactly it really and like I think some people could think that you you know you're not doing experiments if you're doing simulations um but it's just like it really kind of hurries along the step and helps you understand even more um there's never a drug that would kind of go out that has not been tested in the lab extensively um but I think it's really interesting to allow people even like a lot of um medicinal chemists can you show them a simulation

and they can incredibly smart I can just see the molecule and be like I know it's going to interact into this area um but it really helps with things like that as well and it's like it's quite a nice Bridging the Gap between a lot of different fields and so I think that it kind of it's I think it's really really interesting to see how it all kind of comes together and um especially now people are doing so much cool stuff with these computational simulations and

comparing exactly with experience and finding that it just gives like when you test it against the same thing like the same results so it's a really kind of robust method that I think is only going to get better when especially like there's better computational power people can run things from longer and have better kind of do more repeats and do some more stats on it and it kind of is all fitting together really nicely in this huge Information Age yeah it's fun what you say about uh

like different disciplines coming together because I thought that you were a physicist and now you were on about testing things in the lab and I'm like she's come to biology she's come to my side I've won her out I think I know I I think it is funny when my family ask me they're like what is your PhD on and I'm kind of like hm DNA and they're like what are you doing and yeah know it's a it is very multi disciplinary and I'm learning a lot about chemistry which has been quite

difficult for me because as you say I I definitely my masters and my degree was in physics and so to learn I don't know even how to draw Mo a molecule I was like this is Con to me um but it's helping me I think it's really interesting is it's nice to try and have some Physics skills that are coming in a little bit useful absolutely I do think it's all like we've split it purely for our own enjoyment really and very much everything is interl so it's good to have a multidisciplinary

approach yeah definitely because you know I guess people have their perspective as well so you you might have seen it from one perspective and learning a bit of chemistry would help you in your I mean back in the day everyone was was a polymath you know they they just studied everything and then who was I think like there was a physicist who also got a chemistry Nobel Prize because the two were so linked um you know in the in the what I call the Renaissance of the 19 unds

where everyone was learning about atams and that there you are Emma wow to think how far we' come in your future we can't wait I'm hoping I'm hoping I'll keep on working on these these ad yeah if not we at least got some new drugs yeah exactly we win around yeah on that note I think that's a good place to leave it on a nice positive note uh Emma's going to be a future Nobel Prize winner um but before that she's helped us understand a bit more about antibiotic

resistance how we kind of ended up with that but also how how we might overcome that issue with clever planning about discovering Alternatives about how we use antibiotics today and then finally the future of computational simulations and how they will all help towards shortening that drug development timeline so thank you for listening and hopefully we'll have you with us on another episode by the views expressed in this podcast belong entirely to the person that said them they did not

represent any industry or organization if you enjoyed listening to these views it would really help us out if you could rate US leave a review and tell a friend this podcast was sponsored by no one but if you're interested in funding us to continue to have Frank discuss questions about science and engineering please get in touch [Music]

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