The Antibiotic Resistance Crisis: Basic Science to the Rescue | Irene Iscla | TEDxSMU

[Music] scientists we start our careers out of curiosity we want to know how the world around works especially as working in basic science which is research that is not immediately related to a practical outcome something like a treatment or a device but actually it's very very exciting when we can provide any use for humanity with our work and this is the case of a project that I've been working on for the last ten years here at UT Southwestern Medical Center in Dallas I'll dr. Paul blunt group and this is a very important project because it consists it concerns the antibiotic resistant crisis and this is a very serious global crisis it is causing actually 700,000 deaths a year and it is predicted to kill more than 10 million people a year because of untreatable antibiotic resistant bacteria and as you know antibiotics are used to kill bacteria they will not do any good if you use them for treating the flu or the corona virus and the problem is that most amongst bacteria are becoming resistant to them we cannot kill them anymore and this is a very serious problem but the way this happens is with the mechanism of natural selection it's a something we cannot not have this will happen this is how nature works and the way it happens is that with when organisms reproduce they actually make some mistakes or errors in their DNA so in any given bacterial population you will have some bacteria that are already antibiotic resistant then you treat them with antibiotics and then the antibiotics will kill the sensitive bacteria and the bacteria that are not sensitive will grow and produce an antibiotic resistant population and the problem with bacteria is aggravated not only because they reproduce very fast but also they can transfer genetic material to one another so bacteria that have never seen an antibiotic can add choir activity resistance and this is a major problem because we use antibiotics not only to treat infections but we also use them for preventing them when we make surgeries or most modern medical procedures like heart surgery transplants even chemotherapy so if we lose our antibiotics we are going to lose the ability to use these life-saving procedures and this is not something new because or that we didn't know about because Alexander Fleming who actually discovered penicillin the first used antibiotic warned about us gonna warn us about this because he knew that he had seen it his love that if he treated with low doses intere of antibiotics some bacteria some of them will become resistant and not dying anymore so there is the process of antibiotic resistance it's always going to be there because it's the way nature works but we can make it happen much slower if we use the right doses and also if we use them as little as possible only when needed but we're not doing a great job about this because actually 80% of all antibiotics sold are used in animals we are feeding our life stalks our antibiotics and the main reason is not to treat sick animals but also to be able to raise them in very confined and chronic conditions like in the factory farms and also something is called a growth promotion if you give very very low doses of antibiotics to animals they grow a slightly faster and this is actually the recipe to make antibiotic resistant bacteria so there are countries that are legislating this including the us but we have to do much better because antibiotics are really life-saving drugs but we are also we have a lot of room for improvement in our human use because we are actually over prescribing hours antibiotics the CDC latest data says that 30 percent of all antibiotics prescribed have been unnecessary and it's staggering that in the urgent care facilities about 46 percent of antibiotics prescribed for respiratory diseases were unnecessary so we have to take care of antibiotics better there are efforts and in the supership campaign to make better use of them but this is a global problem so it's not something that only the United States can solve and this has to I encourage you to go to the CDC and look at how you can be aware of how to protect these drugs but then another idea is why don't we make a new drug that ant about that and bacteria never saw and that's it the problem is it's not a DC and actually in the last 30 years the antibiotic approvals having only declined and the main reason is that it's not a very attractive product for the pharmaceutical companies because it is very expensive to put a drug on the market and antibiotics aren't things that you had to prescribe as little as possible so they haven't been interested in these but there is one more data that is very interesting that it's since 1987 in a new drug a new antibiotic targeting and a new targeting bacteria with an drug with a new mechanism of action hasn't been released and this is when basic science comes to the rescue because our research even if it's not focusing on these sometimes it can bring new tool to solve a crisis for example I didn't start my career thinking about developing antibiotics I actually wanted to be a park ranger but in my country at the time it was impossible for women to do that so I settled for biology and while I was doing biology I became fascinated by this fact every living thing every creature from bacteria to us are equipped to sense perceive the world around us and respond to it and so because of this curiosity I ended up studying the sensor how sensory inputs will modulate the outputs the motor output and movement in leeches and I studied their neural circuits and this got me a PhD in neurobiology but then I came here and try to understand how they make kind of sensors and molecules that can sense and respond to force work and these are cell proteins they're channels and as you might remember the cell is the smallest functional and structural unit of life and it's defined by a membrane and it was both inside and outside the membrane is exquisitely regulated by channels and transporters and they will open and allow some ions go in in and out of the cell as well as nutrients right this particular channel is a mat mechanosensitive channel so it's a channel that it's in the cell membrane and opens with force and mechanosensitive channels are the basis of our senses of hearing touch balance and also play very important roles in ecology over regulation in kidney function and even in depression but the particular channel I came to study is a channel from a bacteria it's called mechanosensitive channel of large conductance and this channel we know a lot about it it was a first clone channel that had a Meccano sensitive function but the main feature is its the biggest poor known and this is how it compares to the poor that opens every other channel so channels usually are very precise on what goes in and out of of them they even can distinguish between different ions but this sport is huge and they the question is why would you like if you're a bacteria to have such a huge pore open right and the answer is you don't actually this msel is a channel that is designed to remain closed and only open in case of an emergency and as I told you before everything senses better their environment from bacteria to humans and actually bacteria are very sensitive of how things how much things are diluted or concentrated around them and this is called osmolarity so imagine you're a bacteria it suddenly rains the things around you become very diluted the water rushes into the cell makes them swell and the tension in the membrane is what is going to make msel gate and it gates and immediately releases solids and reaches a nuclear and the bacteria survive we know this because we can actually remove msel and when we do that with an iPhone hyperosmotic shock that we call this the bacteria die but then there is a very important thing that we observed from the beginning if you mutate this channel and make it gate when it doesn't need to but did I really don't like to have this hole in them and bacteria die or grow very slowly depending on the mutation you make so they gave us idea this might be an antibiotic target if we make a msel activator we can generate a new antibiotic and there are a couple of things about them a Cllr good for these because it exists only microbes so if you generate a drug target in msel it's probably going to have a low chance of having side effects another thing is it has all of the bacteria especially all infectious bacteria how these channels so if you generate the drug against this channel probably can treat many different infections and a third thing that you might not know but most antibiotics only kill bacteria if they are growing if they don't grow like for example tuberculosis that stays in your body not growing they are extremely difficult to treat and this is they stay in what is called a quiescent state and because msel is present in all stages of bacterial growth we predicted actually a drug targeted will kill bacteria that are not growing so the good thing is we use a Western have access to many resources and among these to a library of 200,000 compounds and what we try to do is to find a molecule that will kill the bacteria only if they have a messy L M msel activator and the ones that we can produce that didn't have a messy L will not die so we wanted something specific okay we want to try to validate a target and actually we found them and so we found it for e.coli which some some strains are pathogens for humans and as you can see we found that do nothing for the bacteria that has that do not have a messy L but they do kill or slow the growth of the ones that do have it and this was the same for Staphylococcus aureus that they produce quite nasty bacterial infections in the skin as well as a cousin of tuberculosis that it's model study so this is in growing bacteria but what about whyisign bacteria in question bacteria will find the same actually we can kill bacteria that are not growing which is a really extra bonus for any kind of antibiotic but lately and this is very exciting too we thought okay what if also not only we can make bacteria sick because we open msel but maybe you can facilitate other antibiotics to enter so we can probably even give lower doses of some antibiotics that are toxic along with this msel activator and make these antibiotics were better and we actually found this true for several antibiotics here is the data for tetracycline so if you put the tetracycline alone but today I kind of happy because this is a very low dose but if when you combine it with the msel activator we find a much much bigger effect so we actually could validate an antibiotic target and probably have it also as what we call an adjuvant something that potentiates the effect of other drugs so my message here is that if we as a group that were studying Meccano sensors could find and validate a new antibiotic target I am hopeful that most researchers around the world trying to figure out how to fight this crisis will prevent us to get to these very very horrible predictions of ten thousand to ten million people dying well thank you [Applause]

Channel: TEDx Talks

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Keywords: TEDxTalks, English, Science (hard), Biology, Medical research

Id: UONwJTYZqwc

Length: 14min 45sec (885 seconds)

Published: Tue Apr 07 2020