Bacteria and Antibiotics: Revenge of the Microbes

the earth is 4.6 billion years old but we humans have been here for just the blink of an eye two hundred thousand years only compared to the vast length of time that the earth has been the earth bacteria on the other hand have been on this planet long before we are in fact for that for most of the time on earth bacteria were here they were here before us they breathed life into our world made it possible for us to evolve and we know about we know about the age of bacteria we know they're about 3.6 3.5 billion years old the first bacteria arose we know this because of places like this this is Shark Bay in Australia you can see these beautiful structures that call stromatolites and they are caused by communities of bacteria that formed thin mats and these trap sediments and then they precipitate calcium carbonate you end up having these stacks and these are preserved very well in the fossil record so this is a relatively young fossil it's only three-and-a-half million years old but you can see the telltale patterns of the stromatolite and we've been able to find stromatolites that are at 3.5 3.6 billion years old so I think you're getting the picture the bacteria are very old and when you draw a timeline like this I struggled because it's almost impossible to put humans on the same timeline as something that's 3.6 billion years old I stuck it at the end there few pixels 200,000 years ago compared to this vast expanse of time now when we came on the scenes as eukaryotic cells were single-celled organisms we had a nucleus we felt pretty good about that bacteria did something very strange they bestowed upon us a gift and that was that they invaded us physically invaded our bodies and gave us the means to produce energy and the first person who came up with this endosymbiosis theory actually was probably someone you haven't heard of him for in 1883 he thought you know there are bacteria out there that looks suspiciously like those organs that we see in plants that are called chloroplasts and people after have noted that well there are bacteria out there that look like mitochondria which are the things inside us that make energy so here's a bacteria that looks suspiciously like a chloroplast and there's a chloroplast I don't know if you agree with stem first and this is a vector called Rickettsia which looks very much like mitochondria as you can see so although a lot of people formulated these hypotheses and developed them lynn margulis usually gets the cut of this discovery 1967 well deserved she gave some great evidence but schimper nobody knows as a name and that is because he put his theory in a footnote so the moral of the story is if you have a great idea don't put it in a footnote okay so bacteria ancients they've been around that friendly ostensibly that gave us energy we've been living to a tanning glove with them for so many years but there are 5 million trillion trillion bacteria on this planet that's more than the number of stars in the universe you can believe it and on our bodies and in our bodies not counting those mitochondria 100 trillion bacterial cells right now as we speak that means that you are all ten times more bacteria than human if I said o-ring thought so we're vastly outnumbered so given that it's not surprising that we often wrangle with Beck's here we have problems with them they infect us they make us sick and they kill us quite frequently and with alarming regularity okay so we know the bacteria have been affecting us for as long as we've been human and before animals get bacterial infections - so back to you've always been with us in making us sick the oldest known infection that we've been able to see scientifically is from 9,000 year old bones these are bones that were this is brilliant actually they were in an underwater city off the coast of Israel so these are underwater bones a drowned city of a young and you can see on these bones the telltale marks of tuberculosis infection they may just look like a bunch of holes to you but if you're a scientist I'm not one actually the knows about this sort of thing these are definitely TV holes but you might say okay I need more evidence than that and despite the fact that these bones were under water for 9,000 years they managed to pull out some forensic evidence of Mycobacterium tuberculosis what you can see here is a chromatograph you see that five Peaks signature which is a particularly lipid it's only found in Mycobacterium they found it on a woman's left rib woman's right rib and an infant's bone and you can see the standard underneath showing that those five Peaks superimpose this is proof that this lipid found only in Mycobacterium tuberculosis was present on these nine thousand year old bones that were under water it's amazing story science is amazing this is the culprit Mycobacterium it's useful just to show this because it shows you how small these things are these things are 2 microns in length that a micron is a millionth of a meter and despite the fact that they're so small they can wreak untold devastation on our species and you've probably all know about second pandemic of bubonic plague in the 13 and 1400s decimated anywhere from one third to one one one half of Europe depending on the statistics that you that you believe and this illuminated manuscript from a contemporary Bible shows basically the fact that there's really nothing you can do if you have bubonic plague you've got religion you've got fairy dust and you've got wishful thinking but they didn't understand what caused that they didn't know why they were sick they didn't know how to cure it they couldn't cure it they couldn't prevent it it was a devastating disease and this just goes to show you how how really devastating a bacteria can be and I like this picture because you can't get DNA or lipids off of this illuminated manuscript but you can the artists were so good back then look at the detail on these buboes which are inflamed lymph nodes characteristic of bubonic plague and look at a modern-day case of bubonic plague you can see I think that it really is bubonic plague and this is caused by Yersinia pestis which is a bug that lives in the hindgut of a flea and this is actually inside a fleas hindgut right now great camera work there so it is it is still with us you're sending it past us this bacteria still causes the plague in isolated pockets and under control for now because of antibiotics for now hold those thoughts okay so why are we all here why don't we all dead we should have been extinct millennia ago it doesn't make any sense well we have defenses you all know that we have a very robust immune system I'm teaching immunology to some students and I think some of them in the audience you know he's incredibly complicated we have dozens and dozens of different cells that patrol around looking for invaders we have specific proteins and compounds that are specific for all these different bugs you can get memory so when you see the same bug again you can fight it better it's the most amazing system but still it's not enough to conquer a lot of bacteria this is a picture an antibody just show you how beautiful these structures are these are these patrolling proteins that can find bits of bugs that are alien and go after them okay so why doesn't our immune system do the job we're highly evolved creature us you know we're top of the food chain why can't we fight a bacterial infection alone and the reason is because of what searches cat-and-mouse evolution this is more coyote and Roadrunner evolution the basic truth is that although we come up with these elaborate defenses bacteria can evolve very quickly to outsmart us to subvert us to get around us so no matter how many interesting and wonderful things we develop in our immune system the bacteria are always one step ahead ok and I'd like to illustrate this this concept of subversion by showing you an example of a bacteria that I work on this is I work in urinary tract infection which doesn't sound so good at cocktail parties but it's a very serious disease actually it is the most common infectious disease of the elderly and it were it not for antibiotics this disease would be devastatingly fatal at the moment it's under control so UTI is caused by several different kinds of bacteria this is ester ashiya coli Ecola you've probably all heard of him he lives in your gut he's friendly he's supposed to be friendly he digests your food and he comes out the other end so e.coli normally is free living so this means they like to live on top of ourselves but they don't go any deeper than that they hang out on the top of ourselves and in our gut this is all fine but sometimes these bacteria get into the bladder I'll leave it to your imagination why they get into bladder but ladies have a bigger problem with this and gentlemen miss because of the anatomy and the proximity of these bugs bladder so when the bacteria gets to the bladder something really really strange happens very unusual and it was totally unexpected when this was discovered about a decade ago so this is a micrograph this is from a lab in San Louis the whole good lab beautiful micrograph of a mouse bladder it's very smooth what's a little bit bibley bobbly but it's by and large is quite smooth you infect this mouse with E coli up the bladder look at that this is what's called a pod the scientists do have a sense of humor this is technically called a pod it looks very science fiction and what it is is the bacteria have physically burrowed into the bladder inside the cells and they've going in there they're regrouping they're multiplying they're they're doing their evil things they're getting really big there's a huge colony it's getting bigger and bigger and bigger and you can see that it's so big that it's descending the cell it's making a blister some of you might have these inside you right now actually so so women get lots of UTIs women get lots of infections like this and between infections they think they're okay but a lot of them have these things going on you can probably guess what happens next these things can burst open and reinitiate an acute infection so it's really hard to treat these bacteria when they're in that pod they're nice and safe the immune system can't get to them and about as can't get to them and they're all very cozy and then they burst open and my lab we've shown that other bacteria can do something similar this is enter caucus which is very common Europe pathogen this is a red side view of a bladder cell in red you can see lots of blue bacteria on the top of the cell but you can also see in the side view there there are lots of Enterococcus inside that cell and they are doing very similar things to the e.coli so this is a common strategy that you're a pathogens use to evade the immune system in the bladder and just for fun I'm going to show you this video this is from the Justice lab in the States it's kind of cool so this is the slow release pod leaching these bacteria into the into the inside of the bottom okay now once they're in there in the bladder there honorable again the immune system can immediately get them and who's gonna get them it's these guys these are these purple things macrophages monocytes real fancy word they mean big cells that eat bacteria who've room up they don't care what they are they're tasty they're gonna eat whatever is in there that's not supposed to be in there this is mrs a bacteria being hoovered up by a monocyte but it could be anything so when these ecoli burst out of their pod into the bladder they're in trouble because these guys are scrolling so what do they do well this is really interesting so some some scientists of Anderson and colleagues have shown that normally e-coli is a capsule shape it looks like a tic-tac and on the top panel you can see the characteristic tic-tac shape of an e.coli but underneath is what happens when that pod explodes these bacteria shape-shift they actually elongate and they form these long spaghetti like structures which have two functions the first function is basically mechanical so if you're in the bladder and your host urinates it's like being in a firehose and because you're so small and the pee is so forceful so the spaghetti shape has been shown to allow the bacteria to cling on in there when the host is urinating so that so they don't want to get washed out they want to stay right where they are okay so that's an adaptation the second thing is it's truly amazing the spaghetti shape appears to impart almost a cloak of invisibility to these filamentous bacteria and this is a really cool video from the same lab that showed the pod the Justice lab what you're looking at here those dark grey capsule shaped things are normal shaped ecoli the big green thing has been false colored in green so you can follow it it's a long filamentous form of e.coli and the blue things are the big angry macrophages that are chewing up the bacteria or they're trying to anyway so let's see what happens here here goes the video so they're hoovering them up there who bring them up there hoovering them up Hoover mover Hoover but they cannot seem to swallow that green thing they try the try there they're either not tasty or they're invisible or both we don't actually understand this strange thing that happens but it's very advantageous to the ear pathogen those are just two examples of strategies that bacteria use to evade us and there are countless others because there are so many different kinds of bacteria and there's so many different strategies I couldn't lie could talk for hours and I would never get through them all so what I want to talk to you about now is I want you to picture the world if we couldn't control these bacteria and in this world used to exist they're 1900's in the United States for example they're statistics suggesting that from every 10 people who died three of those people died from a bacterial infection so 30% of people who are dead were dead because of bacteria or complications from bacteria that's a very high number you'd imagine what it'd be like if you you had a child who fell on the pavement and scraped her knee and the next day she was dead because she had the infection that you couldn't stop imagine that you prick your finger on a rose in the garden and a week later you're dead because you just there's nothing you can do nothing imagine what that would feel like and keep that in your mind okay so this is our Savior penicillin you've all heard this story it's worth saying again isn't it because Alexander Fleming actually gave a discourse I'm honored to be here where he once stood he did it had the famous accident and this is actually a photograph of his petri dish the famous petri dish that was growing bacteria and accidentally got a spore of mold on it and then that's the thing on the top the big white thing the small white things are bacterial colonies and the big black hole between them is the zone of exclusion where the bacteria could not grow because the mold was secreting something that stopped them to kill them and that was of course penicillin his famous discovery but Fleming really couldn't do anything but he tried he published it he tried to work with it it was very complicated and he eventually abandoned it I just want to point out that similar techniques are still used today it's very quaint but the zone of exclusion is still used in diagnostic labs what you're looking at here is a petri dish that has been spread with a sample from a patient and each of those white discs is impregnated with a different antibiotic and then the plates allowed to grow and you can see what happens some of the disks cause bacteria around them to die really well and there bacteria are sensitive to the antibiotic other discs you see are completely rubbish they're doing nothing and some are sort of middle fair-to-middling you wouldn't want to use that in the clinic either so this this is antibiotics and the discovery so so what so what is what is an antibiotic well it is a chemical structure it's approach it's a chemical compound that's produced by a mold or bacteria or another living organism and this is penicillin G it's a beautiful molecule it's very very simple some bacteria some antibiotics are very complicated this one is really simple you can see the most salient feature here one should look at is that four membered lakh tamarang in the middle I think you can see it so this is penicillin G it was a real bear it's hard to isolate it was hard to make useful and an Florey and chain shared the Nobel Prizes Fleming for the discovery of penicillin because without those biochemists and their teams we never would have been able to mobilize this drug and actually if it wasn't for pharmaceutical companies and sort of the war effort we wouldn't have got penicillin out as quickly as we did in the 40s that's Penniston has it work well it's kind of a really nice nice nice strategy so what you're looking at here is the cell wall of a bacteria so bacteria are enclosed by a rigid cell wall and this cell wall needs constant maintenance constant DIY and that is because bacteria are not static they have to divide into so that the cell wall is always shifting and changing and you need somebody there to make sure that the wall is always sealed and that's what this protein called DD transpeptidase does it's a long word there it's just that they're grade that gray shape DD transpeptidase what it does is it mortars together the bricks of the so wall and it's always on duty making sure that there's no holes in it because if there is any holes or chinks in this armor the bacteria will die very important job okay so what does penicillin do comes along it's this yeah this orange thing in this picture it's simply docks with DD transpeptidase in a particular place and gums up the works and that enzyme is now no longer able to maintain the cell wall it's a simple binding and blocking strategy very clever so penciling goes in blocks all the transpeptidase the cell wall loses its integrity and the bacteria dies it's really nice that's just one antibiotic we have lots of them there's lots of potential targets so if you're a bacterial cell you have to do certain things to stay alive and we know what those things are you need to metabolize you have to reproduce your DNA make proteins and you do need to maintain those cell walls so this is the scary picture you don't be able to read it this is just demonstrating the different kind of antibiotics that we have and where they're targeting bacterial cells I materials read it just appreciate that there's a wide variety of antibiotics all going after different aspects of what the cell finds crucial for survival and I have to point out that the cell wall is a great target because on the outside it's like the ramparts and also it's quite difficult to get drugs inside some bacteria so the so wall has been the obvious target but there are other targets as well so after the discovery of penicillin was this guy have you heard this man Salman Waxman most people's not heard of him he is he is a hero he discovered single-handedly 20 different antibiotics in the Golden Age of antibiotic discovery which was between 1940 and 1960 this guy was a soil guy he liked the soil he liked the bacteria in the soil like the moles he was a biochemist he put together strategies and methods for isolating antibiotics from the soil microorganisms not making antibiotics himself but finding natural products that were out there and if it were not for this man and many of us might not be in this room because our parents and grandparents wouldn't be alive he discovers stuff too myosin which was the most amazing antibiotic and he discovered many many more Salman Waxman don't forget his name so now what I'd like to do is I hope I can read this because I'm a little bit excited I would like to read you from note from Alexander Fleming's Nobel lecture because it has a little story is very prescient and very pertinent ok then this is because Fleming was already a little bit worried about his amazing discovery he was worried that it wasn't going to work for very long so I'm gonna have to have a frame they'd have to back off and read this but I would like to sound one note of warning penicillin is to all intents and purposes non poisonous so there is no need to worry about giving and under overdose and poisoning the patient there may be a danger though an under dosage it is not difficult to make micros resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them and the same thing has occasionally happened in the body it's 1945 so it reminds you the time may come when penicillin can be bought by anyone in the shops or off the internet I added that bit I'm sure he would have said it if you think and there is a danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant here is I've had that hypothetical illustration mr. X has a sore throat he buys some penicillin and gives himself not enough to kill the streptococci but enough to educate them to resist penicillin he then infects his wife mrs. X gets pneumonia and is treated with penicillin as a streptococcus to penicillin the treatment fails mrs. X dies who is primarily responsible for mrs. X death why mr. X who's negligent use of penicillin changed the nature of the microbe moral he says if you use penicillin use enough it's a brilliant story I feel a little bit sorry for mr. X it's not completely completely as well but his his fear this is 1945 his Nobel lecture speech came true the same year a little bit afterwards as words start to filter down from the Front's of World War 2 that soldiers were picking up resistant strains of gonorrhea and syphilis from ladies like this they they look friendly they look clean with enough so penicillin was released and the community as a drug and instantly resistance developed okay how does this happen it's just evolution basically you have a petri dish or a body infected with a white bacteria one of these might mutates become resistant to a drug if you treat with that drug all the white ones will die and the red ones will propagate it's actually very simple and it happens in the lab all the time so what is the molecular nature of resistance it is different for every different antibiotic because every antibiotic is different let's go back to our friend penicillin G you recall it has that lovely four membered ring in the middle some bacteria produce an enzyme called beta lactamase and beta lactamase that's a very simple functions it just snips that ring up and this is like that Peniston flops open it's no longer the right shape and it can no longer dock with DD transpeptidase and gum up the works one little clip penicillin is neutralized and it's really easy for this enzyme the gene that encodes it to be passed around so beta lactamase is a serious problem it's made a lot of the penicillin family resistant useless actually to some patients okay now there's more than one way to be resistant to penicillin there's another way and this is employed by M RSA which is of course the evil hospital-acquired methicillin-resistant Staph aureus which is all over the news and it is very common in hospitals and it's sometimes has a beta lactamase but it has an additional defense against penicillin and their family members what it does if it says okay you're gonna gum up my DD transpeptidase I don't care I'm gonna make another one I would make a different DD transpeptidase called MEK a that's exactly the same it's the original version but it's slightly different than penicillin can no longer bind there so the only difference between MEK a and DD transpeptidase is that region where penicillin binds and gums so it basically circumvents the whole problem by producing lots of this other protein which is really devious okay so antibiotic resistance you hear about it in the news a lot and we'll talk more about that in a minute you might think it's something that we caused because you do hear a lot that it's Artful but actually antibiotic resistant is ancient it's just as ancient as antibiotics before we were even on the planet there were bacteria communicating with each other fighting with each other producing antibiotics and producing antibiotic resistance genes it was all going on before we even got here so it's ancient and the oldest antibiotic resistance gene that we've been forensically able to identify it it's 30,000 years ago and back then that's what our ancestors were doing they were making tools like that and just as an aside because I think it's interesting it may be that antibiotics are not actually weapons there may be more communication signals because it turns out that in the wild in the soil the doses of antibiotics that are in there are really low and they're actually not enough to kill things so it could be their primitive form of communication and antibiotic resistance might be a ping you know ping back from that communication interesting slide but we're able to exploit that for now to kill bacteria so how do these genes get around they do get around very very rapidly how does this happen well there's a number of different mechanisms so these are two bacteria having sex and they're connected by a structure and they're freely passing DNA back and forth including resistance genes probably bacteria can also pick up free DNA that's just been left in the environment when a bacteria dies it spews all its DNA out other bacteria can just soak it up another really interesting way the bacteria can get DNA from other bacteria is through viruses so bacteria actually have their own viruses so they're called bacteriophages or if you're British bacteria phages I'm gonna call them bacteria phages some phages for short so phages are basically glorified syringes they go around injecting DNA into bacteria and trying to kill them and this has been going on for long before we were here as well most ancient battles that we just stumbled upon later so in doing this sometimes I don't kill the bacteria something they just inject DNA from another bacteria it's kind of like if you get a mosquito bite and it's bitten your neighbor and now it's coming bitten you and you might get infected with malaria it's a very similar process okay obviously once you have a resistant bacteria in a patient or a person on the tube or on the bus you can spread that bacteria to your friend your neighbor your lover the patient next door the nurse who didn't wash his hands pre-screen patients and this is another great way that antibiotic resistance can spread through the population and obviously in hospitals that's a lot easier so let's talk about hospital-acquired infection this is a very complicated diagram but let's just walk you through it there are two kinds of mrs a this resistant staph aureus the superbug they hear about in the news the one on the bottom is in the community it's actually not a hospital bug it's resistant to methicillin which is like penicillin pretty much and it is resistant because of this blue gene down at the bottom there makes it resistant to methicillin okay it's basically Mecca which I told you about already so this is a sort of relatively benign tame form of resistant bacteria but look at the guy on the top this is from a hospital he's got a very similar genetic structure but he's got more things in it it's a cassette of resistance not only do you have methicillin resistance but you have another gene that confers resistance to another antibiotic you've got this guy here we confers resistant to four different antibiotics so you get six resistances for the price of one if you're infected with this guy so this is why mr s is Odin dangerous it can not only pass resistance genes but it can pass entire cassettes of resistance genes and bacteria doing this all the time okay gets worse it gets it gets worse so the other problem with bacteria is they replicate so very quickly and just to get your head around that I've made a little video in my lab I put some bladder cells in a petri dish nice warm petri dish with some medium and I dribbled a little bit of e.coli on top and I set up the time-lapse video and I just film them so these bacteria are dividing at their normal rate which is once every 20 minutes and you can see that with time this is a ten hour video the bladder cells below become invisible they are so encrusted and covered with bacteria they're just overwhelmed now there's no immune system in this dish and crucially there's no antibiotics and this is what can happen in a patient if there's unopposed oh there's no if these bacteria are not opposed somehow so a colleague of mine Dave Spratt is a microbiologist has a really nice way of thinking about it about how to get your head around this time scale because the more you divide the more you replicate the more you can mutate the more you can pass on genes the more you can get around us he says okay ten days ago where were you you probably could remember you look in your diary 10 days ago was actually 500 generations for a bacteria where were you five hundred generations ago anyone know you were in the Ice Age okay so this gives you a sense of how quickly is back tyria can adapt just got all the time in the world compared with us so ladies and gentlemen antibiotic resistance is accelerating so it's been around for millennia but it's accelerating at a very scary rate and just to illustrate this the scraps a little bit complicated I'm gonna walk you through it what we have is time that an antibiotic was released that's the blue triangle or time it was discovered and the sorry that's the the red and in the blue triangle is the time the resistance was noted in the population you'll see penicillin actually was resistant before was even released as a drug because it was in a laboratory and when they were working with it they noted resistance penicillin did really badly but actually the next few to come along the pipeline were all right you had ten years of grace before resistance was noted the one exception there is a penicillin family member so it's too similar to penicillin um the bacteria already know that one they've seen that joke before so what happened in 1980 suddenly every new antibiotic that was was produced resistance developed very quickly within a year sometimes simultaneously suddenly this ten year grace period was gone what's happening here there's several reasons one minor reason is that we tried to get clever in the 80s and 90s we thought well we understand science now you know molecular biology genomics let's design our own antibodies forget the back to forget the things in the soil let's be clever and come up with our own you know we were rubbish we made we made antibiotics but they were resistance developed like that because bacteria you know they're all over that you know these are ancient molecules you know you don't you don't mess with them the other thing that happen I think you all know this story it's kind of sad antibiotics are being misused at an alarming rate you hear that you hear this all the time you hear it so much that it almost doesn't sink in anymore this whole antibiotic crisis thing we hear it all the time and we'll get back to that too I'll talk about that later we can get antibiotics very easily if you if you don't fancy your chances with a canadian pharmacy online you can go badger your GP till she says yes and people do do this the study was published this year I think that show that I'm British GP is often bowed to pressure and prescribed antibiotics when they were necessary and then once you get the antibiotic maybe you feel better in a few days and you stop taking the full course and that's the worst thing you can do because your edge like mr. X mrs. and mrs. mrs. X you're educating this bacteria to resist you if you don't take the full course if you don't kill them all some of them won't survive a little bit there'll be a bit sick and then they'll evolve that resistance and then the game is up we also have we are soaking our planet with antibiotics aquaculture agriculture livestock there are antibodies are water supply they are educating the whole world's bacteria how to resist our weapons it's like we're giving away the secret plans through our armory to the enemy we just say here it is take it evolve resistance to it and we now have a perfect storm scenario where we have many bacteria becoming resistant to all known antibiotics and the discovery pipeline is completely stalled it's a little bit difficult to read this I think but what you can see here is that in the golden age or discovery between 40 and 1960 20 new classes were discovered there has not been a new class of antibiotic discovered since 1987 except for the one that was reported last week which I'll tell you about it's great timing so three new classes of antibiotics since 1987 and keeping in mind that takes a very long time to go from Moldy Peaches to tablet it could take 10 to 20 years to make a drug out of a discovery this is a discovery void it's been no new classes discovered it's scary there's nothing and this is mirrored by approval rates of new antibiotics you can see here year by year the number of antibiotics that are approved to go down and actually most of these antibiotics that are approved in the past few years they're not interesting new antibiotics they're just riffing off the same old you know penicillin or the same old formula they're just tweaking the side chains a bit the chemists and not making something novel so the bacteria can can evolve resistance to them easier because they've seen something like it before okay so last year you may have seen this alarming report from the w-h-o I encourage you to read it it's free online it makes for some scary reading keeps me up at night sometimes it basically surveyed all the w-h-o regions and asked okay you guys in this particular country how many of your bacteria are resistant to X how many and here's the example at the top you can't really read this but five out of six whio regions are reporting that 50% of more of e.coli are resistant to the frontline antibiotic of choice in hospitals 25% out of hospitals that's 50% of them here in the UK ecoli that causes urinary tract infection 50% of them are resistant to the frontline antibiotic so that's really scary and actually the future that we're all worried about is already here I don't know if you know this but there are now bacteria they're resistant to all known antibiotics this is only a very recent thing if you look at the CDC report from 2013 it's claiming 25,000 Americans dying of infections that can't be treated you've sent to the hospital they do that panel I showed you with all the different antibiotics nothing is killing what's in you there's nothing left they're cashed out there's nothing left these people die usually and it's going to get worse and worse because the problem is growing and we're not doing anything about it which is a theme of this talk okay so why aren't we doing anything why is it so hard to make new antibiotics and the reason is money it all comes down to money and facts are cheap new and pay ten thousand pounds for an antibiotic drug like you would for a cancer drug you don't take it every day like a statin or a beta blocker you take it maybe once a year once every five years you take it for two weeks you don't take it every day for the rest of your life so it's not a very profit oriented thing and people like to trash Pharma for not being altruistic enough to do things but you know without money you can't do research and the vast majority of drugs you develop as a company don't even make it onto the market at all and the net the stat here shows that basically the antibiotic is worth negative fifty million dollars at the onset it's not their fault and also regulations are really bad they have been really bad it's a lot of red tape it's not easy to get a new antibiotic onto the market there was a few scares of a while back and there was an overcompensation and basically it's very difficult and I'll so to be fair as a scientist it's hard we found all the easy fruit the low-hanging fruit Salman Waxman Nick them off with his 20 antibiotics those are the easy ones and it wasn't easy I'm telling you it was hard but antibiotics are hard they're hard to purify the heart to make they're hard to find so we need new ideas I were quite desperate for new ideas so what's coming down the pipeline well this combination therapies you've probably heard of Cola moxie clav you heard of this Co moxie clav is basically to 205 in one it's a it it's a penicillin like drug but it also has an acid that we stops the beta lactamase from clipping that ring so if you put them in together you restore the ability of the antibiotic to work it's a nice idea okay this is kind of retro so phase therapy if you heard of phage therapy so last century we all decided in the West to go down the antibiotic route very expensive the Soviets couldn't afford it so they decided to look at bacteria phages as a way to fight infection and then people have noted that if he's bathe in the Ganges which was really polluted he got really sick but then were resistant suddenly to a lot of different bacterial infections and people realize that sages were out there killing bacteria and this is this is really cool idea so in Georgia in the former Soviet Union you can go to the doctor and get prescribed Payoh bacteriophage which is a bottle full of bacteria phages really I'm not getting dozens and dozens of them in a bottle and it's so funny because the bacteria are evolving resistance against the bacteria phages very quickly I mean they replicate you can fasten the bacteria do so twice a year these guys in Georgia have to refresh the recipe but to go out and find the latest pages throw away the old bottles make new bottles it's almost like our flu vaccine every year we have to change a bit twice a year you've got to change these bottles I think it's a really nice idea and a lot of people are looking into it because we're running out of other ideas okay this is a little bit more science fiction this is Christopher Cass which is a fancy name for a DNA that you can design that will go into bacterial cell and find an antibiotic resistance gene and nuke it so suddenly the bacteria is missing its resistance to yoonho and then you can hit it with an - addict so you're basically curing them of resistance this is a little bit further down the road because we have to work out how to get those DNA's into the bacteria it's like gene therapy is little bit difficult you have to design is really specific DNA is its you have to understand all biology but it's a really nice idea and this came out last year - a lot of headline news which you may have read but really people are thinking you know we need to go back to the soil there are so many bacteria out there and and I don't know if you know but how many bacteria in the soil can actually be cultured in the lab any guesses percentage-wise 1% 1% 99% of molds and bacteria and things in the soil won't grow in the lab imagine how many antibiotics they might be hiding in there those treasures that we cannot grow so this this this this was a gift to the Friday evening discourse speaker last week in nature a new class of antibiotic was discovered after you know since 1987 and it was the most amazing paper so beautifully written paper it's actually quite technical but I think you might even be able to get a glimmer if you read it yourself it's been made open access so everybody can read it this is so important a new antibiotic kills pathogens without detectable resistance how do they find this antibiotic they did this is amazing I wish I thought of this it's such a simple idea they took a lot of soil bacteria instead of growing in the lab they just buried it in the ground and left it there and then they dug it up and lo and behold all these bacteria were growing all these moles are growing all these things for growing that would never go in a lab like what a great idea and then they were able to use very classic methods to quickly isolate I assume it was quick isolate brand new species of bacteria and brand new antibiotics and this is this one here here this they called the soil hotel this is a soil hotel overlaid with sapphires look for that zone of exclusion and isolate the compound take so backed in you'll probably hear this word again it's a it's a beautiful very complicated antibiotic compared with penicillin a lot of them are the beauty of this guy is that it fights bacteria you know in a different way it doesn't fight proteins like beta lactamase proteins are really easy to evolve resistance to because you just need a gene it fights a lipid lipids are not encoded by genes to inactivate a lipid you have to make a lipid you have to do lots of different genes and lots of metabolism and it's really complicated it's hard to find one place where you can actually fight that there's another antibiotic out there called vancomycin if you heard of this vancomycin was an amazing was an amazing ant about it because it resistance seemed never to happen because it's against the lipid as well it fights a lipid and only recently vancomycin has not become resistant resistance has arisen and it was a bit of a fluke accident actually it's a long story I won't tell it but this guy also fights lipids and it's a great hope because the author's tried to find things were resistant to the center-back they couldn't find anything looked everywhere not a sausage so hopefully if we treat this antibiotic with care it will last us a good 10 20 30 years and unfortunately it only acts against a certain kind of bacteria the ground positives which leaves a big gap for the gram negatives like e.coli and other big killers but hopefully this strategy can be used generally maybe not just the soil maybe we can go to the deserts under the oceans all different environments and find all these new bacteria grow them in their environment without where they like to grow so this is a brilliant discovery just I'm so happy that I was around to see it ok so another problem that we have with there's nothing to with resistance is biofilms have you heard of biofilms I mentioned by Phil's at the beginning the Easter medalists are caused by matt from biofilms if you scrape your teeth right now something comes off that's a biofilm of dental bacteria slimy rocks that's a biofilm biofilms are everywhere it was only recently appreciated that most bacteria are living in these communities and they're not free living at all and this is just a schematic showing that these bacteria come together in groups very complicated groups and they form these primitive organs almost they secrete this slime and the slime protects them from antibiotics and other other things and it's estimated now that in the US it's causing a massive problem with healthcare because these things grow on catheters and indwelling medical products and they're actually involved in a lot of infections and they're very difficult to treat because they're slimy can't get the antibiotics in there and the other thing they do is when they're in that community they're exchanging DNA lots so they're they're exchanging resistance and they're making the problem worse so we need to solve this problem as well just for fun my lab is growing biofilms in love this is a beautiful video from one of my students you can see what are you looking at it's just a thin section of biofilm the top these red things are metabolically active bacteria the green things the middle are sort of structural things that aren't growing very much and there's this channel because it's blue channel or water and nutrients can come through it's a really beautiful structure and what we're trying to do now I'm collaborating with engineers in Oxford and at UCL we're trying to make nano capsules and microcapsules that can penetrate biofilms because it's no good having an antibiotic that works if you can't get that antibiotic inside to where the action is so I think that collaboration between biologists and physicists and engineers are another thing that we need to get out of this mess so we're in trouble as a species I think and maybe I've convinced you that we're we're in trouble but I'm interested just finally in the final few minutes my talk where is this complacency come from it's not that we haven't heard about this hundreds of times before you look at this media survey 1961 in Good Housekeeping which is a girlie mag they were talking about antibiotic resistance and I don't overuse them for casual reasons and every generation since now and then has founded this a lot of Fleming sounded the alarm everyone's having this hysterical headlines guys were in trouble and nothing happens um there's a great happens in our country too so in 2013 the chief medical officer said guys it's like climate change and terrorism rolled into one few headlines I want quiet the next year David Cameron medical dark ages few headlines went quiet Cameron he said this thing which just made me laugh he's announced to review and to why so a few antimicrobial drugs have been introduced in recent years we don't need a review we know we've known for generations that is difficult they are the incentives the money is we know we don't need a review what we need is money and effort put into this problem and the US Congress is doing great with cutting red tape to help I think we've got initiatives they use throwing money at it UK's announced a strategy so I'm sure it's very good and of course the longitude fries is giving permanence prominence to antibiotics but what we really need Mr Cameron if you want to write your MP you can tell them what we need is money because seismic research is very expensive and we spend hardly anything on it if you look at this lovely graph from science to Graham you can see that the UK is at the bottom of the developed nations for spending money on science is point five seven percent of GDP then even the point seven nine that's the g8 average it's a pitiable amount of money to spend in research and development for something as important as science because we need science not just for antibiotics but for climate change and for food security all these problems that we have to solve we need science to get us out of this mess and we're spending pittance on it so I think you should all write your MP and tell them you're gonna vote in the next general election what do you think about science so just in conclusion keeping in mind it takes ten to twenty years from discovery to tablet we have a discovery void aside from this wonderful nature paper that ruined my story no no needed new classes discovered since 1987 we're still in trouble with gram positive and gram negative organisms given that we need we need to put more effort and we need to stop just shrugging it off I think we've had too many crisis stories oh the the bacteria are coming the bacteria coming I'm not helping I know but it really is time to get serious we don't go back to the age when we're all dying the bacteria are one step ahead of us and we need some to catch up now some immunodeficient patients recommended antibiotic prophylaxis and I was wondering why those patients don't become overwhelmed with resistance bacterium and why doctors choose to do that

Channel: The Royal Institution

Views: 43,282

Rating: 4.8876753 out of 5

Keywords: Ri event, bacteria, antibiotics, antibiotic resistenc, disease, infections, biology, Science, Ri, Royal Institution, science communication, Education, microorganism

Id: nmGaq9DsUfo

Length: 46min 43sec (2803 seconds)

Published: Wed Mar 04 2015