I’m Willem van Schaik, Director of the Institute of Microbiology and Infection at the University of Birmingham. I study how microbes become resistant to drugs. Ask me anything!

Thanks for doing an AMA! I have just started a PhD in Microbiology studying antimicrobial resistance in the food chain and would be very interested to know your opinion on antibiotic usage in farms.

In your opinion how much does antibiotic usage in the foodchain contribute to AMR in the human microbiota? The literature seems to be quite divided on this issue. Also, do you think that we can defeat AMR solely by stewardship of existing antibiotics or will we require new formulations or alternative therapies?

Great question and something I have actually done some work on :)

As you probably know 80% of the world's antibiotics are used in agriculture. Sometimes that use is perfectly valid (e.g. to treat mastitis in cows) but sometimes it is really problematic (e.g. as 'growth promoter' -> antibiotics increase growth/yields of farm animals with a mechanism that we poorly understand: this practice has been banned in the EU since the early 21st century, but it is still in use elsewhere).

As any use of antibiotics is likely to lead to resistance at some point, what we do in agriculture is create a massive reservoir of antibiotic-resistant bacteria and antibiotic resistance genes. The bacteria themselves may not be too much of a problem as bacteria are generally very well-adapted to the host. For example E. coli from chicken will have adapted to growing at 41 C, which is the body temperature of chicken, but is likely outcompeted by those bacteria that colonise humans (growing at 37 C).

However, the really tricky bit is that some genes that confer resistance to antibiotics are located on mobile genetic elements: pieces of DNA that can be exchanged readily between different bacteria. So, that E. coli from a chicken may not cause an infection in a human, but it may transfer its resistance genes to the E. coli that is present in the human gut. This might be the reason why some very high-profile resistance genes (Extended-Spectrum Beta-Lactamases [ESBLs] and Mobile Colistin Resistance [MCR] genes) have spread quickly: they were strongly selected for in agriculture through antibiotic use and then transferred to bacteria that were adapted to live in humans.

To quantify all these risks, however, is really difficult. I think there is now a consensus that most antibiotic resistance that we see in hospitals is caused by human use of antibiotics, as that directly selects for resistance in bacteria that have adapted to live in or infect humans. However, some of those resistance traits can be coming from animal reservoirs.

Hope this is (a bit) clear. Happy to expand further!

Do you think the Tory’s apparent resistance to cocaine is contributing to the saner parts of Britain from fully eradicating the Tory infection, or does the UK like being a gangrenous zombie of a nation run by coked out automatons?

Can I subscribe to your newsletter?

So.. biofilms! From what I understand, many bacteria that cause us problems do so because they form biofilms. Somehow these function as a shield against our immune systems & medicines. This makes me wonder, were biofilms a somewhat recent evolutionary development? Or are they in some way something our immune systems can't touch because they are 'out of their league'? Do you think disrupting biofilm formation might be something that comes to human antibiotic medicine soon?

I love biofilms! They have been around pretty much for billions of years: it is just a great way for bacteria to (literally) stick together and they are much less likely to be killed by microbial predators (amoebae) or immune cells. Antibiotics also don't penetrate biofilms well so... Disrupting biofilm formation is really difficult because they are so sticky (think of plaque on your teeth: you can only remove it by brushing; very difficult to do when somebody has a urinary tract infection!) . However, interesting progress is being made (also by colleagues in the institute) to develop materials that are intrinsically antibacterial and/or prevent biofilm formation. These could be used for implants, catheters etc.

(@powerdns_bert here) So I will get my question in early :-) With the COVID-19 pandemic, we've seen how powerful our techniques are for figuring out how viruses work, how they interact with cells and how we could block them. See the stunning success against hepatitis C. If we look at the relatively small genomes of bacteria, which are also rather well documented, would it not be possible to invent like "thousands" of new antibiotics that get transported into bacteria (because they look like things that bacteria would import) and that also block vital processes within these bacteria? And hopefully leave us alone of course. I realize nothing is simple of course, but if I see what we are throwing at COVID-19, it feels like we could have found several new antibiotics alone this year if we did the same thing for bacteria!

The COVID19 pandemic is certainly showing how successful large, international teams of scientists can be in testing therapies against the virus. However, finding completely new drugs or developing vaccines takes a lot of time. Indeed, the drugs that now work against COVID19 (primarily dexamethasone) have been repurposed, rather than developed from scratch over the last few months.

Your idea to develop drugs that can be transported into bacteria is excellent. Indeed, people are studying this, right now! For example, iron uptake system can be used for bacteria to take up antibiotic-siderophore complexes (siderophores are products made by bacteria to capture iron from the environment) https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(18)30315-X/fulltext. I am not entirely sure how far this is in clinical development, but it could work. However, as with all antibiotics, bacteria will develop resistance to these systems in the long-run (e.g. the uptake channel might mutate slightly). Other transporters are very specific for specific compounds so it might be difficult to have them take up that compound linked to an antibiotic (which is generally a fairly bulky chemical).

I note that we very often prescribe exactly one antibiotic at a time against bacterial infections. However, for viruses we have learned to use 3 so they don't evolve resistance. Why don't we do this for bacteria then, is there a fundamental reason? Thanks!

Great question. The crucial difference between bacteria and viruses is that viruses can only evolve resistance through mutation, but that bacteria can become resistant by mutation and process called horizontal gene transfer. So in viruses, you would be extremely unlucky if it evolves resistance to three antivirals at the same time, but in bacteria you can also have the bacterium acquiring a bit of DNA that contains resistance genes to multiple antibiotics in a single event and you would strongly select for this possibility by giving multiple antibiotics at the same time. Bacteria also have systems called efflux pumps that just pump out the antibiotics that are in the cell before they can do harm, so by giving three antibiotics simultaneously you might strongly select for bacteria with increased efflux capacity.

I have read prognosticators who warn of a "post-antibiotic age" where AMR is endemic worldwide: routine surgery becomes highly risky, people die of easily treatable infections, etc. Grim stuff.

Is AMR a threat like climate change, where we're on course for such a world unless we make drastic changes now? Or are those predictions exaggerated, meant to inspire change but not likely to actually come to pass?

I think it is in the same category of 'future threats that we can start acting on now, but won't'. Climate change is probably worse than AMR though as resistant bacteria will not cause the icecaps to melt...

Some reports claim that AMR will cause 10 million/deaths per year in 2050, but I think that is a worst case scenario. However AMR already causes ~35,000 deaths in the EU per year and that number is gradually climbing upwards. The situation in countries like India and China (>2 billion people!) is however, considerably worse already, so we do need global, concerted action now to (a) minimise unnecessary antibiotic use and (b) develop new antibiotics and other interventions (like vaccines) against multidrug-resistant bacteria.

Thank you for doing an AMA! I'm not well versed in anything microbiology related, but have been casually looking through the history of drug resistance and what little information I have found has been both frightening and jaw-dropping.

Can you please ELI5 how a microbe can continue to develop immunity to more and more of our developed antibiotics? Is it theoretically possible for them to become immune to every drug over time? If so (or close to all drugs) does this force them to develop weaknesses to other threats such as heat/uv etc. Its scary to think of an unkillable bug. I'd assume evolution pushes something to be stronger in one respect by adapting but force it to give up something else.

Take care and be safe.

In the end, antibiotic resistance is the logical outcome of the evolution of microbes. Because they can replicate relatively fast (certainly compared to humans!) there is a fairly high chance that they will accidentally develop a mutation that, for example, changes the target of an antibiotic, thus making that specific mutant resistant to the antibiotic. Because all other cells, which do not have the mutation, will die very quickly in the presence of the antibiotic, only this mutant will survive. Bacteria can also develop resistance via a second mechanism: they can take up DNA from other bacteria via a variety of ways. Sometimes that novel DNA contains a gene that encodes an enzyme that breaks down an antibiotic, so the bug again becomes resistant. So, yes: it is possible for bacteria to become resistant to all antibiotics, and scarily this is already happening (google for pan-resistant Klebsiella). It is very difficult, however, for bacteria to develop resistance against physical traits, because those you cannot inactivate with an enzyme. You can teach bacteria to become a bit more resistant to UV or heat or ethanol, but this can only be done to a relatively small extent (e.g. becoming a bit longer (a few minutes) or a few degrees more heat-tolerant). So: antibiotic resistance is a real problem, but bacteria cannot overcome all physical barriers!

I've seen the recent campaign from the University of Birmingham about the use of a honey derivative as a substitute for antibiotics. The example given on the university website is for use in wound cleaning. What makes these kinds of substitutes different from existing products? Are we overusing antibiotics where "blunter", less selective tools may be effective?

It is definitely true that we sometimes reach for antibiotics while other treatment options are potentially effective as well. Honey has all kinds of antimicrobial compounds (peptides, enzymes that produce reactive oxygen species that are harmful to bacteria) that could act as part of wound dressing. However, for many infections it is difficult to think how we could use honey (or other disinfectants): in a bacterial pneumonia, you cannot pump honey into somebody's lungs!

Hi Willem! Thank you for doing this AMA. Question: do you think that coating everything in copper due to its antibacterial properties could be counter-productive in the long run? Could some bacteria eventually become resistant to copper? Thank you for your response!

Worryingly, there are bacteria that combine copper resistance genes with antibiotic resistance genes... So I am not too keen to coat everything in copper (or silver or other metals) as that is very likely to co-select for antibiotic resistance.

Hi! I’m a nursing student currently taking a medical microbiology course. Very excited to be able to pick your brain!

I am of the understanding that antibiotic resistance is a result of selective pressure, and that misuse or overuse of antibiotics helps accelerate this problem. As a future nurse, what is something that I can do in the clinical setting to help prevent this?

Thanks for your question. Unfortunately any use of antibiotics can lead to resistance, but, of course, when we want to treat an infection in a patient, we are very happy to take that risk. But misuse and overuse should certainly be avoided (e.g. in viral infections antibiotics should generally not be used as they only act against bacteria). Hospitals should have strong 'antimicrobial stewardship' programs that set out policies to minimise overuse and misuse. I cannot really comment on how those work in your specific setting, but your colleagues should be able to tell you. And if an antimicrobial stewardship program does not appear to exist, perhaps you should try to set it up with your colleagues!

Are bacteriophages really as viable as this Kurzgesagt video makes them out to be?

Are superbugs really as dangerous as they sound?

Are we all gonna have to go through this quarantine shit again when superbugs dominate the world?

I do not have the time to watch the Kurzgesagt video, but I have responded to a question on phage therapy above.

Superbugs are pretty bad, particularly if you are young, elderly or immunocompromised (and we will all be one of those three things at some point in our lives). They already cause ~35,000 deaths/year in the EU alone.

Because of the rapid spread of antibiotic resistance there is a real concern that we may no longer be able to treat infections in the future or perform surgeries that are currently routine because of the risk of infection with a multidrug-resistant bacterium. However, these bacteria do not spread as easily as a respiratory virus like flu or COVID19 so you won't have to go into quarantine when antibiotic resistance becomes even more widespread. Perhaps you may have to undergo tests to determine that you are free of superbugs before hospital visits in the future.

Could a fungus eventually adapt to kill a drug resistant bacterium? Like if you left a colony of penicillium and penicillin resistant bacteria together, would the penicillium eventually find a way of neutralising the bacteria?

That's a fun question and an interesting Gedankenexperiment. I think the fungus will simply overgrow the bacterium and kill it by other means than penicillin. Fungi make lots of different antimicrobial compounds (only very few of those can be used as antibiotic in humans as many will be toxic to us). So, the fungus will produce its full arsenal of antibacterial compounds, of which some will help kill the the resistant bacterium. As it has no need to evolve a slightly different penicillin, it will not do this.

Thank you for doing an AMA! What are some of the most exciting approaches for combating AMR in the near future? What are the biggest challenges in their implementation?

That is a big question! I would say that an approach that is likely to be most successful is probably also very dull and un-sexy: just using as few antibiotics as possible and implementing evidence-based infection prevention in hospitals. Northern European countries are showing that by doing this, you can minimise the risk of antibiotic resistant infections. However, these can be quite costly and even in countries like Norway or the Netherlands where they have very good health care and strict antibiotic stewardship/infection prevention policies, there is a gradual but clear increase in the number of drug-resistant infections. So, we definitely need new drugs and I really like the idea of coupling those to compounds that are taken up by bacteria (see my reply above here somewhere). There are also some exciting developments in screening novel bacteria for the production of antimicrobial compounds (remember that most antibiotics are natural products) which is providing some interesting leads. However, the development of antibiotics is quite tricky economically: it is expensive and pharmaceutical industry will not make a large profit (remember that with antibiotics, you take them for a week, you get better: job done, not much money mode; other drugs: you take them for the rest of your life: $$$!) on new antibiotics. There is also the risk of rapid resistance development by bacteria (they evolve quickly).

Thanks for doing this!

As a fellow academic (but am in the social sciences) with experience living and working in the UK and NL: what has surprised you most about the COVID government/public responses in both countries?

Personally I found the UK response depressingly predictable in its ad-hoc/short term-ism and opportunism. I am much more surprised however in the non-pragmatism of various Dutch policymakers . In some way the endless "poldering" was perhaps predictable, but I am genuinely surprised in the ongoing scepticism towards e.g. face coverings.

...and to the extent you feel comfortable disclosing, any general thoughts on working in Dutch vs UK academia?

I've worked inside and outside academia in multiple countries, but I find the ubiquity of three letter acronyms in my UK institute, often related to admin, really quite bewildering and frustrating.

First a disclaimer that I am not an expert in public health, political science or behavourial sciences so this is just me talking as an individual rather than putting my official scientist hat on.

The UK was very late in locking down in Spring and I found that very disconcerting as it was clear that the pandemic was spinning out of control and social distancing measures should have been implemented earlier. Indeed, I spoke up in the media when other European countries (including NL) locked down by ~13 March, while the UK locked down 10 days later. One very positive policy in the UK was the rapid expansion of testing capacity, but unfortunately that was not linked to effective test, trace, isolate policies so that capacity could have been used a lot better. In NL, there are still problems with testing as far as I know, so that is certainly something that has not gone well there. The really odd discussions about face masks in NL have also surprised me. While I was also not entirely convinced by their effectiveness in March, I think by April it was becoming increasingly clear that even reusable cotton face masks could make a difference in the spread of COVID19. I still do not understand why the Dutch government and policy makers have not embraced those insights much earlier.

I can write another 1000 words about working in Dutch vs UK academia, but I probably won't. Good things about the NL are that it is all a bit better organised, but the funding situation is pretty poor, while in the UK there are many options for funding (still very competitive of course, and of course, unlikely to have access to EU but let's not go there). In the UK it also appears to be slightly easier to move outside your own field and start collaborating with different disciplines. So, not at all unhappy that I made the move, but I could do without a pandemic and no-deal Brexit!

Oh yeah, I also hate the acronyms and abbreviations!

Hi! Is page therapy the future of tackling all sorts of AMR?

Phage therapy is super-exciting but there are three issues:

1. phages are very 'host-specific', so almost every bacterial strain has its own phage. So you may first need to do laboratory checks to determine which phage attacks the bacterium causing an infection. This takes money and time (and that time might not be there if a patient is very ill with an infection).
2. it may be difficult to give phages systemically (e.g. to treat bloodstream infections) as they might not bump into the bacteria that cause the infection and/or can trigger all kinds of immune responses that you might not want to see.
3. As always: bacteria will develop resistance to phages. Bacteria have many anti-phage mechanisms (CRISPR-Cas being the most famous one) and it may be difficult to circumvent these.

However, some really remarkable studies (like this one) have been performed with phage therapy so it may be possible to overcome some of these problems (but, in my opinion, it is still unlikely that it will be a silver bullet that can be used in the treatment of all bacterial infections!). More research is needed, I suppose!

I hope I’m not to late for this. First off thank you for doing this AMA.

My question pertains to the development of new antimicrobial therapies.

As we know the US particularly has a very capitalistic mindset when it comes to healthcare, and because of this there seems to be a running theme that it’s financially a better decision to treat a disease so that it no longer functions than it is to cure it. A good example of this is HIV and AIDS. Obviously the medications to treat those diseases are not only expensive, but are 100% required to survive. However curing the disease would be counterproductive from a fiscal perspective because a cure is “one and done.” Beyond that, due to the side effects of many of the treatment medications, it creates a secondary market for medications like antiemetics.

My question is this, given the pushback we’d likely see from pharmaceutical companies in developing a cure, do you feel like we will ever find said cure for diseases like this, and if so why?

I don't know the situation too well in HIV drugs, but I don't think there is evidence that 'Big Pharma' is withholding a permanent cure to HIV. Indeed, because HIV is very sneaky in the way it hides in our immune cells, you probably will always need to use multiple drugs simultaneously and/or cycle through different drug regimens, to minimise the risk of resistant populations evolving.

Some pharma companies (but not many) are still developing antibiotics. To be honest, it is a painful process as candidate drugs can work great in a petri dish, but don't have good pharmacodynamic/pharmacokinetic properties, are toxic or bacteria rapidly evolve resistance to it. There are many examples of companies sinking tens, if not hundreds of millions of dollars, in antibiotic development and in the end not developing any viable new antibiotic. I am reasonably optimistic that the few pharma companies that are still in this field, particularly medium-sized ones, will come up with new drugs against the most problematic multi-drug resistant pathogens over the next decade or so. However, remember that we have then won the battle, but not the war: bacteria will undoubtedly evolve resistance to any newly introduced antibiotic... In my opinion, antibiotic development should thus be a continuous process rather than a one-off investment.

Is it possible bacteria can get resistant to non-antibiotic means of killing them? Could there ever be "soap-resistant bacteria" or "cooking-resistant bacteria"?

I think I explained this below somewhere. Bacteria can evolve mechanisms to inactivate certain compounds, like antibiotics, but it is far more difficult to evolve meaningful resistance to physical stresses, like high temperature.

So I read that bacteria can transfer resistance to each other. How can they do this?

The three most important mechanisms of DNA transfer (or 'horizontal gene transfer') between bacteria are:

- conjugation: bacteria transfer a plasmid (a small piece of mobile DNA that replicates independently of the chromosome) to a neighbour

- transduction: a bacteriophage (a virus that infects bacteria) takes a bit of DNA from a bacterium it has infected and moves it to another bacterium that it infects.

- transformation: DNA molecules are directly taking up from the environment by a bacterium

Of these three, conjugation is probably the most important for the spread of antibiotic resistance genes: there are many plasmids and some can be quite promiscuous (spreading among different species of bacteria).

Hello Dr. William, I am an undergrad student and currently working on NDM-1 antibiotic resistant bacteria. For now, my job entails writing a review paper on the topic and would like to work on this further. I wanted to ask that we don't know the origin of blaNDM-1 gene, how can we fight against it? I also wanted to ask about antimicrobial peptides as an alternative to antibiotics since gram-negative bacteria are also developing antibiotic resistance and we don't have any concrete methods to fight them? I am very interested in this topic and hope to work on it in future. I hope that I get lucky enough to work under your supervision!

blaNDM-1 is a very cool (but scary) resistance gene. I have not stayed up-to-date with the literature on its origins, but I am expecting it to come from an environmental bacterium and that it has then 'jumped' into human pathogens like E. coli.

To fight against it, I think groups are developing inhibitors of NDM-1 activity (this could be an interesting article) that you could give in combination with e.g. a carbapenem, so that the bacterium would still be killed. I don't think these have reached the market yet, but I could certainly have missed something.

Antimicrobial peptides are sometimes proposed as alternatives to antibiotics, but they are generally quite tricky to work with: they can be broken down by proteases, they generally are not very soluble in e.g. human serum (so can't be used systemically) and they are very 'sticky' (meaning that they bind to basically everything, not specifically to the bacterium that they are targeting). It is still an interesting field for drug development, but these problems turn out to be quite difficult to overcome.

And if you want to do postgraduate studies on microbiology in a great university with excellent researchers, why not consider our MSc in Microbiology and Infection: https://www.birmingham.ac.uk/postgraduate/courses/taught/biosciences/microbiology-infection.aspx

Hii! Thank you for doing this AMA!! This is a very strange phenomena to me! How bacteria can share the DNA between species. Something that is so difficult for us and they use it as a way of communicating.

...So, we had a couple COVID patients that where intubated, got rid of COVID, successfully extubated. But, they now where infected by B. cepacia.

We gave double antibiotics (Tigecyclin and Colistin), but, didn't work. Do you have any experience with it? Should we burn the hospital?

I am not a medic, so can't comment on what to do in treating these patients. I assume that these bugs are already resistant to beta-lactams and other, more commonly used antibiotics, as colistin and tigecycline are pretty much used if there is nothing else left. Burning down the hospital seems a bad idea but I do hope these patients have recovered!

What are your thoughts on the gut-lung axis? Are there causative events going on i.e. does the lung microbiome directly influence the gut microbiome and vice versa, or are changes correlated to something else?

I think interactions between the gut microbiome and [other organ] are almost always immune-related. So if the gut bacteria trigger a certain immune response, that will affect what bacteria can grow in other environments of the body. I don't think there is anyway that gut bacteria migrate to the lungs or vice versa (indeed, if they do, you might have a massive problem!)

Hi William, I'm William too!

Do you believe that children, adolescence, young adults that are raised in more sterile environments, (Lysol abundance, extreme handwashing, restrictions on playing outside or with others) may end up more susceptible to falling ill with common bad bacteria? Would you say that bacterial defense comes from being introduced to more bacteria younger, or more from the genes you are born with? Thank you!

Hi William, interesting question. This is essentially called the 'Hygiene Hypothesis' and Wikipedia has a really good article on it. I think there is some evidence that playing outside etc reduces the risk of developing allergies, but I am not aware of convincing data to show that it could protect against bacterial infections later in life.

What's your view on the use of Phages to kill off antibiotic resistant bacteria?

I have already answered a similar question today: you should be able to find it if you scroll up.

Hi, I read a little bit about bacteriophages a few years ago and was really interested at what they had to offer. I’d like to know is research still continuing with them? (Btw I have very little knowledge in this field so if you do respond pretend your talking to a 4 year old)

Yes, people are still studying bacteriophages and they are really cool. Lots of interesting biology to discover. I have covered the issue of phage therapy in the treatment of bacterial infections elsewhere today.

Not sure if you are familiar with “Microban” which claims to have materials that are “resistant to microbial growth” but is this even possible or is it a hoax? For instance some iPhone cases are made with microban and claim they keep your phone case cleaner because of that...

I don't think there is any need to make an iPhone cases out of 'intrinsically antimicrobial materials'. The risk of anyone picking up an infection from an iPhone is very small indeed. It is not a hoax, because the materials work, but I really do not see the need.

Hello Willem. Hopefully you see this question tommorow! I was really interested in bacteria last year and learnt so many cool things. I saw Bonni Basslers TED talk on quorum sensing and tried to read much more about it but i either couldn't find much or it was too academic for me to understand. Its so fascinating to me. In your opinion how viable do you think anti-quorum sensing compounds can be as an alternative to antibiotics. Also is there any progress being made with phage therapy?

Bonnie Bassler is giving a Prize Lecture in our institute in January. Very much looking forward to that as she is a formidable speaker. I am not aware of any real progress being made in 'anti quorum sensing' approaches to bacterial infections. Phage therapy is interesting but also has its own challenges which I have outlined elsewhere today.

Hypothetically if we'd stop using antibiotics all together. Would resistant bacteria disappeare too over time?

Not really as most antibiotics are natural products so are produced by bacteria and fungi in soil. So it is always good to have some antibiotic resistance genes as a bacterium. However, if we stop using antibiotics tomorrow (a bad idea as many people will die of bacterial infections!), it would take a very long time for resistance to go down to 'natural' levels, primarily because the biological cost of carrying antibiotic resistance genes is often quite small.

Have you met any famous people?

I met Stromae (a Belgian artist who sold 8.5 million records across Europe) on the train a few years ago. Have chatted with two or three Nobel Laureates.

How fucked are we due to rampant antibiotic abuse?

Quite fucked if we don't minimise unnecessary antibiotic use and develop new drugs and vaccines.

What Restaurants do you avoid? By type, not name.

Why I ask - I took a season of Microbiology during my college days, and my professor had previously been a state epidemiologist, and would go on these glorious tirades about the restaurant industry for being disease spreaders. This was back in the 80s, but I can still today hear him, in my head, railing about investigations that uncovered epic food safety and worker sanitation issues that made him vow never to go to a restaurant he had not personally inspected.

I go to all types of restaurant (or went, bloody COVID...)

Can we make good bacteria resistant to antibiotics? Is it a good idea?

Yes and no (why would you want to do that?)

What's the ugliest building on campus? And why is it Chem West?

They tore Chem West down last year!

Hello fellow microbiology enthusiast!

I work as a clinical microbiologist at a hospital where a large part of my job is testing organisms against panels of antibiotics.

As I’m sure you know, there are certain drug/bug combos that do not have breakpoint interpretations (we use CLSI’s guide here in the US) and yet my Infectious Disease doctors sometimes ask for us to run certain isolates against these antibiotics anyway. A recently requested example would be fosfomycin against a highly resistant Pseudomonas aeruginosa in a urine culture.

Now, I’m sure there is info out there somewhere about it being useful but I’m just curious where they are getting this info from and whether it would be a good idea to just throw some of these drugs at an infection when we do not have breakpoints established to “prove” their effectiveness. Is this good antibiotic stewardship? Or should we be more discouraging of such requests?

This is probably where I should say that I am no clinical microbiologist so I am not entirely sure whether giving fosfomycin for a Pseudomonas UTI makes any sense. I know that fosfomycin resistance is quite common and can develop quite quickly, but fosfomycin is also a first-line choice for UTIs... So perhaps somebody thought: 'determine the isolate's MIC for fosfomycin and perhaps we're lucky and it has a low MIC'. I think this is actually good antibiotic stewardship: it would be bad if the treating clinicians would simply give fosfomycin without antibiotic susceptibility testing!

Hello, I did my undergrad in microbiology and am trying to decide where/what to do for my graduate education. I know you’ve already called it quits on this AMA but I hope you find this.

For some context, a human baby is born effectively sterile and that the majority of microbiome forming bacteria comes from breast milk and the home environment provided by the parents. Would you consider these “inherited” microbes to play a major role in obesity for a child?

Of course, lifestyle and diet are no doubt the core contributors for obesity, but there have been plenty of studies (at least in mice) confirming that microbial transplants have direct effects on metabolic function and resultant fat storage. I tried to keep this all very surface level; this topic really blooms when you start getting into specific in vivo bacteria populations and their direct role in various metabolic processes.

Interesting question! I am personally not fully convinced that disruption of the microbiome in early life (e.g. due to C-section and/or antibiotic use) has a major effect on the risk of obesity later in life. The data from mice seem clear, but translating these insights to humans has turned out to be quite complicated. There is more evidence that allergies are correlated with microbiome disruptions in babies.

And if you are thinking about post-graduate studies, perhaps you can consider Birmingham ;-)

How do you see how covid will be stealth with incoming years? Will it be something completely cured or something you fall ill of and then go to hospital for treatment. And what do you think about the possibility of another pandemic happening a long time down the road

I expect that there will be a vaccine in mid-2021 that will protect most from serious disease. It is, however, too soon to say if this vaccine will also be effective in the elderly. Older people generally do not respond as well to vaccination as the young, so we might have a situation that those that are most at risk are not protected... That would be pretty bad. I also think that treatment will improve, but for now the most important thing is that healthcare systems are not overwhelmed, because in that case it is almost impossible to provide high-quality care.

And yes, there will be other pandemics. Remember that we have had flu pandemics every 20 years or so (2009 was a relatively mild one), and we are still living through the HIV pandemic (30 millions deaths so far). The next pandemic will probably again be a virus, might be flu, might be a coronavirus, might be something I have never heard of. In the mean time, resistance to antibiotics among bacteria will also increase steadily, which formally is not considered a pandemic (mostly because there are so many different bacteria that are involved, rather than a single species) but is likely to cause significant illness and deaths in the future.

I like Earth (it is a great planet) but sometimes it is good to remember that microbes are the most abundant form of life around here and they are not done with us!

What is the worst bacteria to catch in hospital?

Difficult to say as there are so many and it very much depends on the underlying illnesses of a patient. I am personally most worried about multidrug-resistant Klebsiella pneumoniae or Acinetobacter baumannii. These bacteria very rarely cause infections in healthy individuals but they are a real nightmare to treat in patients and resistance to multiple antibiotics is very common in these bugs.

Goeiemiddag!

They've found antibiotics that can treat MRSA, any idea how long it will be until it becomes resistant to those?

My son takes clindamycin every day for a MRSA infection in his spinal hardware. Very tough situation all around as antibiotics wreak havoc on the system, but his body can't handle another spinal surgery to clean the hardware. We are trying to "contain" the infection for as long as possible. The infection becoming resistant to the clinda is my biggest fear.

I am very sorry to hear that, and I understand your concerns. A good thing to remember is that for MRSA there are many more antibiotics available than for some of the other bacteria I discussed here today (like K. pneumoniae and E. coli) so even in the (probably unlikely) event that your son's MRSA strain develops resistance to clindamycin, there are probably other options. I hope you can discuss your worries with the doctor that treats your son. My best wishes for you and your son.

Very difficult to say! But historically, we generally found resistance to new antibiotics emerging 1 - 10 years after their introduction.

First things first. What is the evolutionary origin of bacteria?

So let me answer that one a bit to give Willem a rest. If we trace back the evolution of all life we end up at two starting points, both bacterial in nature. There is a common set of genes and functionalities that must have been present in these two oldest ancestors. RNA (one of the two ways of storing genetic material) was already there, but there are hints it might have been interpreted differently at the time. For example, currently three RNA letters describe an amino acid, there are hints that "way back when", two RNA letters might have done the job. But in any case, as far as we can tell today, the very first living things on earth looked like and then morphed into the two kinds of bacterial life we know today.

I am not an evolutionary biologist, studying the origin of life, but I think the above is correct. One interesting thing about the evolution of eukaryotes (essentially humans, plants, animals, fungi etc) is that they arose because a bacterial cell started living together inside an other bacterium. That bacterial squatter became our mitochondria: the power plant of our cell!

What do you think is the current biggest gap in public understanding of AMR and how can this be addressed?

It is difficult to make a broad statement here as I am limited to my own, personal experience in the UK and the Netherlands. I would say that generally public understanding of AMR has improved tremendously over the last decade or so. The main gap might be that people think that humans themselves can become resistant to antibiotics and not the bacteria. From a policy perspective, this might not be too much of a problem as the behavourial outcome is positive ('only use antibiotics when needed'), but it takes away the understanding that people can spread antibiotic resistance via their bacteria: it is a collective problem, not an individual issue (like COVID19). The solution could be to make it clear that bacteria populate our body (indeed, our bodies have about as much bacterial cells as human cells!) and, fortunately, they generally contribute positively to our health. If we use antibiotics, it is possible that some of them become resistant and that could be an issue if these bacteria cause an infection.

how true is it that if we don't take the dose as recommended we might render certain antibiotics inadequate in future sicknesses?

is it true we should stop flushing antibiotics down the toilet? (i havent done that, but have heard it can be an issue)

Don't flush antibiotics down the toilet: they will end up in the environment and select for resistance there.

The discussion on how long you should take antibiotics (e.g. for 1-2 weeks or 'until you feel better') is a really complicated one. The evidence base for taking an amount of antibiotics for a set period of time is sometimes surprisingly weak, but that also does not mean that you should stop taking antibiotics when you feel better as there might be residual populations of the bacterium that cause the infection left and those will grow out again. The best advice is to follow the advice of your GP or other medical professionals and take antibiotics as long as they are prescribed (and don't self-medicate with antibiotics). Studies on the optimal duration of antibiotic therapy are ongoing AFAIK.

Thanks for doing this AMA! What's your favourite bacteria and virus?

I don't really have favourite bacteria and viruses: I love them all, I suppose.

But I am really quite fascinated by bacteria that started out as fairly innocuous commensal bacteria and have quite rapidly become multidrug-resistant pathogens, like Klebsiella pneumoniae and Enterococcus faecium.

My favourite viruses are bacteriophages because they kill bacteria :)

Hi! I am a medical student and currently i am studying microbiology and sometimes its hard to memorize all the names of bacteria and viruses and other microbes and also how they cause pathogenesis. I oftenly mix up one type of microbe with another one. So is there any fun way to study and memorize all this stuff so that i can’t forget it?

I don't think so sadly... One thing you may want to remember that you do not need to memorise the names of all ~30,000 named species, but only those that cause significant morbidity and mortality. There are a couple of mnemonics that could help, e.g. ESKAPEE describes some of the most important multidrug-resistant opportunistic pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter, Escherichia coli)

I think Willem meant "you do [not] need to memorise". At least I hope he did.

Yes, correct 'do NOT need to memorise'! Have edited

Thanks for doing an AMA, im intersted in the topic and looking for an end of study project, I'm currently studying ingineering in biology , is there a way to have an internship working on this project as in my country we really lack research facilities and it's pretty hard to find a great topic like this?

You can always drop me an email (address on website in my announcement) but I have to say that this academic year (and perhaps the next too), it will be hard to host students on an internship as we have to prioritise our own students and because we need to socially distance in the lab to minimise the risk of transmission of COVID, there is not a lot of space left to host guests unfortunately.

Hey there, thanks for doing this AMA!

Fun question: what are some of your favorite facts that you wouldn’t be able to find with a simple google search?

Are there facts you cannot find using Google??

Can you explain what you do in a ELI5 thing? And also how do they become resistant to drugs? Do different microbes have different ways of becoming resistant? Do you like donuts?

There are many ways that bacteria can become resistant: they can have random changes in their DNA, which, for example, slightly changes the structure of a protein that is a target of antibiotics (making the bacteria resistant to antibiotics). Bacteria can also transfer pieces of DNA that carry genes that inactivate antibiotics (e.g. by cutting them in half or chemically slightly changing them): after acquiring these 'antibiotic resistance genes' these bacteria also become resistant. I am particularly interested in this process (we call this 'horizontal gene transfer') There are many ways bacteria can become resistant to antibiotics: it is not simply 1 gene or 1 mutation and that is why it is such a fascinating topic of study.

I don't go out of my way to have donuts, but don't dislike them either: I am a bit meh about donuts, I suppose

Med student here, first year so I don't have much technical knowledge. But if I may ask, what are the risks that we may run out of antibiotics? What can we do to prevent this, if it is at all possible?

The risk is very real: indeed, in a small number of bacterial infections we have already run out of antibiotics to use, or we have to use antibiotics that have bad side effects (e.g. permanent hearing loss, kidney damage)

To prevent antibiotic resistance from spreading further, we can do the following:

- Use antibiotics wisely: don't misuse and overuse antibiotics in human medicine or agriculture

- Prevent infections (e.g. hand hygiene)

- Develop new antibiotics and alternatives to antibiotics (e.g. vaccines)

Hi Willem! Thanks for doing this! I understand that bacteria can become resistant to antibiotics - but can viruses become resisitant to biological defences like white blood cells or even hydrochloric acid?

Viruses will be inactivated very quickly by hydrochloric acid: it's nasty stuff!

Some viruses can actually invade white blood cells and kill them from the inside. HIV is the most famous example of a virus that does this very efficiently.

Can you recommend any documentaries or YouTube channels which you would recommend so that people can understand what researchers such as yourself are doing?

This page has some great resources. 'I contain multitudes' by Ed Yong is also highly recommended.

Is antibiotics being used by incompetent people to treat viruses a major problem, and if so, in what way would it be possible to spread the correct knowledge to stop it before more people potentially get hurt because of resistant bacteria?

It is definitely a problem! There have been some very successful campaigns to minimise inappropriate prescribing of antibiotics (e.g. in the case of a viral infection), for example this one so that is a positive development.

This is a super interesting AMA! My question is, how easily does antibiotic resistance spread between countries and around the world?

Quite easily, as humans travel the world, picking up and transporting resistant bacteria: it is quite well-documented that travel to Asia is associated with people becoming colonised by antibiotic-resistant bacteria. We also transport animals (cows, pigs etc) across borders and rivers also have a role in spreading resistant bacteria in the environment.

Why was my Microbiology class in college so damn hard?

Microbiology is quite hard: bacteria, fungi and viruses are very different from other life forms that you can observe without a microscope!

I was wondering about the lung microbiota. In the gut it is already common knowledge that there are many good bacteria. And there already exist gut bacteria to swallow. Would something like that be possible for the lung? Like inhale some typical good bacteria for the lung? Could this be an aproach to get the lung microbiota in a better balance or even help against resistant bacteria like make them weaker?

It is still a matter of debate whether the lung microbiota is a thing. In the gut there are trillions of bacteria that are closely packed together, while in the lungs the numbers of bacteria are much lower and spread out over an incredibly large surface (the surface area of your lungs is roughly the same as a tennis court). I don't think we need to actively change the composition of these bacteria in the lungs by inhaling them and, if the experience with probiotics in the gut is anything to go on, it is unlikely that bacteria that are artificially 'added' to the lungs will become members of the lung microbiome for long periods of time. They will likely be outcompeted by bacteria that are already there.

I’ve heard a little about resistant strains of fungus like C. Auris. How big of a concern are those and what’s in place to stop them currently? How might researchers approach creating new antifungals?

Fungi are actually overlooked a bit as important drug-resistant pathogens, which is weird as they cause many, difficult-to-treat infections. Because fungi are more closely related to us than bacteria are, it is more difficult to develop good antifungals that are not toxic to the human host. C. auris is a massive concern, particularly when there are outbreaks with this fungus in hospital among patients with weakened immune systems, as it has evolved resistance to multiple antifungal drugs.