230: Ancient bacterial DNA

This Week in Microbiology is brought to you by the American Society for Microbiology at asm.org slash TWIM. This is TWIM, This Week in Microbiology, episode 230, recorded on November 12th, 2020. I'm Vincent Racaniello, and you're listening to the podcast that explores unseen life on Earth. Joining me today from Small Things Considered, Elio Schechter. Well, hello there. Nice to be with you.

Always a pleasure. At the distance. I presume you're still sheltering in place, right? Am I ever. I'm totally sheltered. I couldn't be shelterer. Also joining us from... Ann Arbor, Michigan, Michelle Swanson. Hello. And it's a beautiful fall day here, blue sky. And then we've got a lot of orange and golden leaves, mostly on the ground. Hey. I talked to someone in Utah the other night and they have snow on the ground. We're going to hit 50 today.

Yeah, we have this rainstorm. It's just pouring. Also joining us from Charleston, South Carolina, Michael Schmidt. Hello, everyone. Where it's still summer. We're having us yesterday. We had thunderstorms and we have a hurricane coming up. Another one. And, you know, hurricane season ends in two weeks on Thanksgiving, but it continues. It just continues. We're almost through the Greek alphabet.

We've already been through the Phoenician alphabet, and now we're starting after the Greek alphabet. Michael, I'm sorry to say, but you're the only red state amongst us. That's true. That's true. We have three blues and one red. But Charleston is a blue enclave in all of the red. A blue, dark, and a sea of red. Yes. Is that the only blue in South Carolina? No, really where the universities are, are blue.

The University of South Carolina and Columbia is a blue zone. Charleston is a blue zone. And. There is limited blue around Clemson, but for the most part, it's very, very red. Wow. Interesting.

All right. Let's move away from politics and get into real good stuff. Microbiology. And Michael is up with a snippet. Well, since we're getting towards peak poultry eating season. and I mean Thanksgiving, I thought we would discuss this really exciting paper.

that appeared and applied in environmental microbiology this November about protecting this very important... protein source especially as families prepare meals from this very common protein source in the human diet namely protein as many of you are aware consequence of getting the chicken ready for sale often results in the raw chicken meat becoming contaminated with a gram-negative microbe, Campylobacter jejuni. at levels ranging between 10,000 to a million microbes per chicken carcass.

This is in spite of heroic efforts on behalf of the meatpacking plant, the USDA, and all sorts of other regulatory agencies as trying to keep the meatpacking plants. clean using disinfectants, developing all sorts of protocols to try to rid the chicken carcass of these microbes. And the fact of the matter is all of the interventions that they have tried at the plant candidly don't work. They work in the lab, but they're unable to drop the load.

10 to the 6 microbes per carcass is referred to as a log 6, and 10 to the 4 is referred to as a log 4. When you can only drop things a half a log or one and a half logs in practice, That means that chicken still has a lot of these very infectious and virulent gram-negative microbes. What do they do to you, Michael? How do they make you sick? What's the disease?

They basically cause gastrointestinal upset. They give you diarrhea, stomach cramps, and in significant cases, they can actually, you develop Guillain-Barre syndrome. which is a condition that begins with tingling and weakness starting in your feet and legs and can spread to your upper bodies and arms. They also can cause a... reactive form of arthritis. And unfortunately, like many other enteric gram-negatives, microbes, an increasing proportion

of human infections caused by campylobacter are resistant to antimicrobial therapy. And Michael, this must be a global problem because I see that we have authors from...

three different countries that contributed to this. Absolutely. And I was just about to introduce the title of today's talk and the authorship. And we'll just go straight to the authorship. They're from the University. of British Columbia in Vancouver, Canada. The King Saud University in Saudi Arabia.

Washington State University here in Pullman, Washington, and McGill University, which is also in Canada. And the paper that we're going to... quickly go through today is called active packaging of immobilized zinc oxide nanoparticles controls campylobacter jejuni in raw chicken meat. And it was authored by Hakeem, Fang, Nigaz, Ma, Say, Konkel. And as I said, they're from a multi-institution consortium. And this is truly a collaborative activity. Now, the first thing we need to know.

It's not the chicken's fault. The chicken itself gets contaminated by this microbe, or I should say in... the true sense of the thing, the chicken's intestine gets colonized by Campylobacter jejuni very early in its life. And this is irrespective of its free range. or organically grown, or antibiotic-free, this microbe, Campylobacter jejuni, colonizes the chicken gut. It's normal flora for our poor little chicken.

And in fact, poultry in general. And in the commercial raw chicken meat, that's... offered for sale in North America and Europe, they found that between 70% to 90% of the meat that's sold for retail is indeed positive for Campylobacter. And so our epidemiology friends have shown that poultry is indeed the main reservoir and root of transmission of this really nasty bug to humans.

And if this news was not bad enough for the consumer, this microbe can readily form biofilms. And this is why you've often heard about the importance of sanitizing your cutting boards. And the handle of your wooden knives, because the microbe can actually embed itself and effectively start growing a biofilm.

on those knives unless you properly sanitize them either by aggressive washing with soap and water or running them through the dishwasher. Unfortunately, cooking kills this, right? So this is the reason we're... This is the reason we're all upright. I'm sure like most of our physicians, they're telling us to eat less red meat and more poultry because it's better for us.

You know, I often when I introduce the subject to students, I say it's very important to cook your chicken. And I said, if you don't really appreciate why, ask yourself the question. why haven't you discovered chicken sushi? And the reason is, is because the majority of chicken meat is indeed contaminated. And no matter how well we try to... harvest the protein from the animal, invariably, because of the anatomy of the bird, it gets contaminated by the campylobacter.

Yeah, I was shocked when they said 70 to 90% of commercial raw chicken is contaminated with campy. Oh, yeah. It's incredible. So in spite of all of this.

Our authors here today are going to introduce an intervention. And they're going to do this in the form of nanotechnology. Nanotechnology is one of these buzzwords that we hear about if you read the National Science Foundation call and all these other places. Nanotechnology simply is at the scale of the microbe. And what they are going to introduce us to is metal oxide nanoparticles.

as potential candidates for food packaging applications. Now, we've all bought, you know, prepackaged chicken, and we often find that that boneless... chicken breast or the chicken thighs or the legs or the whole animal comes on an adsorbent pad. And that's what they're going to do. They're going to actually incorporate zinc oxide nanoparticles into those adsorbent pads that absorbs the juices that are naturally leaking out.

of the chicken that would then serve as a medium that would facilitate the contamination of our kitchen, our cutting boards, ourselves, our hands. And zinc oxide... is a stable antimicrobial. that inactivates microbes by several mechanisms. This is a multi-mechanistic approach to death in the microbial world. And it principally is a derivative of the...

Fenton reaction. And some of you recall that iron undergoes a Fenton reaction and you generate free radicals, reactive oxygen species and reactive nitrogen species. This is principally due to the fact that iron, copper, zinc, aluminum all live in the middle of the periodic table as transition elements. And this transition element means they can accept and...

donate electrons to these reactive molecules and form these, if you will, molecular grenades that go off and kill the bacteria. Michael, is the... So the mechanism is similar or not similar to copper? It's similar to copper. It's not as efficient as copper, but it's the same mechanism. It's a derivative of Fenton reactions in which we're getting superoxide derivative, oxyanion, nitric oxide.

And all of these things go off. Maybe we should put copper mesh pads in the thing and that's it. That could work. That'd be expensive, I guess, right? Well, not necessarily. If they can be reused and you can autoclave metals just fine. Now, the other thing that we have to appreciate that zinc oxide particles. falls into this magic category of compounds that is classified by the US Food and Drug Administration.

as a compound that's generally recognized as safe. And in the pre-show, Vincent was asking me, what do we have to do to demonstrate that we can safely use these materials? Do we have to do toxicology studies? But because the FDA recognizes this molecule as safe, you don't have to do... A lot of the studies that you would anticipate because it's recognized as safe by the U.S. Food and Drug Administration as well as the European community as well. But the particles themselves are not.

Grass, right? No, the particles themselves are not grass molecules. Zinc oxide is, but nanoparticles. And the authors go to great lengths in their paper addressing... that the nanoparticles remain fixed to the adsorbent material. And they have two particular figures with EMs that highlight that the nanoparticles stay where we put them. But the little voice in the back of my head tells me, you know, how sure are you that it's 100% out to six decimal points that it's really holding on?

That's a discussion for another time. So let's go now to actually looking. First, they actually make the three dimensions. They did some really clever things. The first thing they did is they made a three-dimensional paper tube. in order to figure out the minimal bacteriocidal concentration that the immobilized zinc oxide particles could inactivate the camphilbacter.

And they use principally 25 part per million and 50 part per million and 100 part per million concentrations of nanoparticles. And for those of you... who think in molar concentrations, that's 308 micromolar, 617 micromolar, and 100 ppm is 1.2 millimolar. And the bottom line is that at 25 ppm, they knock down 90% of the population. At 50, they knock down greater than 99% of the population. But by 100 part per million, they were able to reduce the concentration of bacteria.

And how quickly? I forget. How quickly was that? That was within the timeframe of, I believe, in that particular experiment. It was... What was it? It's in their supplementals. And unfortunately, I don't have that number in front of me, Michelle. It's days, not just minutes, right? It's days. It's days. They figured out the concentration. They figured out that this was for pure culture, campylobacter, but they wanted to move into the absorbent pads.

And so they did another clever experiment similar to what we do with antibiotic sensitivity discs. And they were able to work that out. And they gave us a glimpse. into how the functional pads and zinc oxide were getting along with the bacteria. And take a look at how they did it because it's really... Pretty clever. But since this is only a snippet today, I want to get to the practical experiment, namely.

They're absorbing pads. Will they inactivate a campylobacter cocktail on raw chicken? So they went to great lengths. They bought chicken at the local grocery store. then incubated it overnight in the refrigerator, and they put 10 to the 4 bacteria of the Campylobacter. onto this raw chicken and then they placed it on this adsorbent pad and they used two principal concentrations of zinc oxide nanoparticles in the adsorbent pad. They use 70.075 milligrams per centimeter.

or 92.6 micromoles per centimeter squared. And then they also used 0.856 milligrams per centimeter squared, or 10.6. micromoles per center meters squared. And what they saw, and this is in their third figure, is the lower concentration. really wasn't all that good at reducing the campylobacter concentration. It really struggled with even taking out any. of the bacteria off of that raw chicken and in fact it took eight

before that lower concentration was able to even drop the concentration a smidge. One point. four or five logs, which is just a smidge. If you're considering 10,000 bacteria, you're only dropping at a thousand bacteria. So that's not much. But the next concentration that they evaluated, the 8.56 milligrams per centimeter squared, that was...

very effective. By day three, which was the first time point that they assessed, you can see from their figure that they went from four to just over two logs of activity. And then by day five and day eight, they were in the weeds. They were at the undetectable level or greater than four sigmas of what's actually going on there. The other thing that will either disturb people or will give them some sense of gratitude that the nanoparticles aren't really doing anything bad to the protein.

is lactobacillus and sycrophils. Again, this chicken was stored in the cold, either at four degrees or seven degrees centigrade. when they did the experiment, is lactobacillus continued to grow on the raw chicken meat. And in fact, its concentration increased and the sycrophils actually increased. up to seven logs in concentration. So this is encouraging that we're only taking out... the bad actors, if you will. We anticipate that the sycrophils and the lactobacillus will eventually...

alter the protein that we're going to consume. And remember, lactobacillus' principal end product is acid. And that's effectively a cooking process that some of us are familiar with. And that's ceviche. As you treat protein with acid, you can effectively cook the flesh. And so it's a really clever experiment. But the bottom line is these absorbent pads did indeed reduce the concentration of the pathogen that makes the majority of us sick. Now, next up.

They asked the question whether or not the zinc nanoparticles were escaping from the adsorbent pads. And they show us an EM. to show us what it looks like. And they effectively deposited nanoparticles on raw chicken, and they show us an EM of what that looks like. And similarly, they took a piece of chicken. off of one of the absorbent pads and they subjected it to EM and simply looked for nanoparticles.

The thing that most people familiar with EM know that zinc is a very electron-dense element that will react in scanning electron microscopy and will light up like a crystal. tree and it was quite evident at least from the figure that they offered us is that there was no zinc oxide particles on the chicken But the one experiment that I was most interested in, given the fact that the lactobacillus was growing, was the release of zinc ions at different pH levels. Because here...

As the lactobacillus grow, the pH goes from neutral to acidic because that's what lactic acid bacteria do. And as the lactic acid bacteria grew, so did the concentration of zinc, divalent zinc, available for the Fenton reaction. So what they showed is that there was a significant release of divalent zinc particles or zinc ions as the... The pH rose and the largest release of zinc in point of fact was after 48 hours.

which was observed at a pH of three. So, and this was in the presence of the lactic acid bacteria. and by refrigeration. So the question is, can we use lactic acid in concert with zinc? zinc oxide nanoparticles to help us preserve our precious protein for sale longer. And then the last experiment that I'm not going to go into detail for because of this being a snippet is they ask the question, what is going on from a molecular perspective? What is exposure to zinc oxide nanopause?

particles doing to the transcription profile of the microbe. And as you can imagine, the microbe is reacting by trying to deal with the oxidative stress associated with the exposure to the nanoparticles. So pretty much that's it in a nutshell. It's copper nanoparticles are reacting. And they are taking out the campylobacter, which should help preserve our poultry for safe consumption. So if we are concerned about the particles, because, you know, people are concerned about...

ingesting these small particles. They can clog small capillaries. They can do problems. So I don't, you know, the EMs are so focused. There's such high magnification. You're not going to really get a good... You're not going to get a 50,000-foot level. And they didn't quantify it. It was just a couple images. So I suppose they have to do some animal experiments to show that.

The particles don't go into animals, right? Feed them some chicken that's been stored in these nanoparticle-containing pads and then see if they pick up any, right? You can probably use... radio tag tracers of the zinc. And ask the question, does the radioactivity move? And this is one of those instances where radioactivity will be your guide because you can put the animal in a whole body scanner and ask the question because the radioactive signal.

will allow you to detect a very small concentration of the particle. And we don't yet know the toxicity profile of nanoparticles in a human condition. The other issue is going through the digestive tract of a human, you go through a very low pH in the stomach. And so the question is, if you accidentally ingest a zinc oxide nanoparticle,

Will it all just become zinc? And then you need not worry. Is the pH of our stomach sufficient? But what happens if you're on one of these proton channel blockers? Will that then... vent your stomach from protecting you. So I think things have to be done to assess whether or not these are indeed generally recognized as safe in the form of nanoparticles.

I think the idea is tremendous, though, that you could put something in the packaging and get rid of this problematic bacteria. That's very ingenious, I think. It was a wonderful study and it just came out in AEM. So I said, we got to talk about it. Nice. Thank you, Michael. I was surprised that you could get logs of killing of Campy and yet the other microbes in the gut.

were unaffected, and even some other strains of Campy were less affected. And that's what's the spooky part of this, is will the microbes adapt and we select out? a zinc oxide nanoparticle resistant variant that hasn't been found for copper and people have been hunting for copper. for a very long period of time. And in fact, copper oxide particles are being incorporated into COVID-19 masks and doing all sorts of interesting things using the same mechanism of action.

Molecular grenades. Yeah, but I agree. It's a really creative and promising avenue of research. Michael, you can make a really great mask and a lot of people just won't wear it. That's true, Vincent. That is true.

Elio, what do you have for us today? Pandemic. All right. Did I get your attention? You certainly did. Okay. That's old news. It's old news. So pandemic is a vague term that says if an epidemic spreads to many places, it's called a pandemic. Fine. Why am I doing pandemic on this week in microbiology, which is mainly bacteria? It's because pandemics, in fact, are not just caused by viruses. They're caused by bacteria as well.

So Victor, you'll allow me to have the subject broached in this particular episode. So here are examples. True that viral infections cause pandemics and mainly smallpox, the flu, measles, yellow fever, but so do bacteria. The plague, TB. Typhus, cholera, all those are bacteria. So here they are. So the important thing I want to talk about is historical. Pandemics happen.

throughout history. And the particular time that I want to deal with is the colonization of America by the Spaniards and other Europeans. When that happens, shortly after the discovery of America, around 1545 to 1550, There were some huge epidemics among the Native Americans, especially in Mexico and in Peru. This was so big that the word decimation, which is cutting...

to a factor of, by a factor of 10, it was appropriate. The population of Mexico went from 20 million to 2 million, best we know, okay? So what was this? Well... First of all, why did the Europeans not get it? If they brought it, why, how come they were resistant? And in a book which many of you, many of the listeners have read called Guns, Germs, and Steel by Jared Diamond, a fantastic book. He discusses the fact that Europeans were probably immune or partly immune to these organisms because...

they were living with cattle. They were cultivating cattle, sheep, goats, horses, all of which were sources of bugs. Whereas in the Americas, About the only large animal that was cultivated besides chickens was the llama and the vicuña in the Andes. In Mexico, there were no large animals other than chickens. There were just chickens. So since these organisms, the bacteria, are probably transmitted from animals to humans,

If you live with animals, you're going to get the bug and you're going to become immune. If you don't have large animals, you're not going to become immune. So that's the idea that this was the process by which... the people in the Americas got sick so badly. Okay, so far, we have a pandemic or at least a large epidemic throughout the Americas.

killing people by the large numbers. So, how do we know, how do we study this? How do we know that this is what happened? Well... There's a thing called ADNA. The A stands for ancient DNA. If you can get ancient DNA and you can sequence it, you can find out what was available, what was present in those days. So how do you do this? Well, DNA is very sensitive, breaks down rather rapidly. But luckily, there are sources of DNA which are fairly resistant to decay.

They're mainly the pulp of teeth of cadavers. If you look at the tooth, the pulp of the tooth is a relatively resistant thing. to decay, and the DNA can be extracted from there. It's not the only place you can get it from bones. You can get it from lesions in bones, for instance. And so there are several ways in which you can study. the DNA of ancient people. Well, it turns out that in Oaxaca, Mexico,

By the way, the place where the epidemic really was an epicenter. The epidemic, by the way, in ancient... North American languages was called the cocolist, they'll translate vaguely into great pestilence. So they found mummies in... places near Oaxaca, Mexico, which is in southern Mexico. And they found that the DNA of the teeth was quite well preserved, considering. So this was a way of studying the epidemic.

The authors of a paper that I'm discussing here, which are just hold on a second and I'll find it. So while you're looking. This DNA is 470 years old. So it's not like from last week. This is old DNA. But it's not the old DNA. It's not called old DNA. It's called ADNA. But it's not the oldest. We've got Neanderthal DNA, right? That is true. That is true, Vincent. Actually.

Yeah. Neanderthal, I think, is the oldest, right? Yes. I think that's right. Yes. Anyhow, there's a paper written in 2018 in Nature, Ecology, and Evolution. The authors are about 12 authors, 1, 2, 3, 4, 5, 6, 7, 8, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 authors. The senior author is called Oschild Vogene. And the senior authors at the end are Kirsten Bose and Johannes Krauss. And they are from various institutes in Germany, mainly in Germany. And let me...

And the National Institute of Anthropology and History in Mexico from the archaeological project of Mexico City, Mexico. But most of the studies, the Institute for Archaeological Sciences at the University of Tübingen in Germany, the Institute of Evolutionary Medicine in Zurich. and Harvard and Mexico City Center for Bioinformatics in Tubingon. Anyhow, these people did a number.

They got the teeth from these people who died in the epidemic. And so they could look and see what they had. What they found was the DNA of salmonella. Paratyphi C. Let me remind you, salmonella, the bad salmonella is paratyphi, causes typhoid. But there are salmonella paratyphi A, B, and C, which cause paratyphus. Paratyphoid, I'm sorry. Not to be confused with typhoid, typhus.

Paratyphoid is a disease which is not found much in Europe, but it is found in other parts of the world, especially Africa and Asia. And it's a pretty bad disease. It's not as bad in general. It's typhoid, but paratyphoid can be bad enough. And in a population which has never seen it, it could be much more virulent than in a population which is used to it. So the idea...

Key point here is that unlike salmonella that we think about with food poisoning, which pretty much stays in our gastrointestinal tract, these typhi and paratyphi get into the blood and they can go systemically. And that's how they get into the teeth because the teeth have a blood supply. So that's why they choose a really great way to capture what had been in the blood. Thank you very much. So you cannot get the...

The Campylobacter from the chicken that Michael was talking about in the teeth. Probably not, right? That we know of. That we know of. But Salmonella paratyphi C is found in the teeth. It was found in the teeth of a whole lot of people, in fact. Let's see, 10 out of 24 individuals. who died and were found in a cemetery near Oaxaca, well documented to have been people who died after the contact with the Spaniards.

The DNA from teeth of people who died before contact of the Spaniards do not have the salmonella. So salmonella is a candidate for the... this terrible disease that affected so many people. So does it prove it? And the answer is no, it does not. First of all, how did they do the study? The study required doing a lot of analysis. And they used a system called MOLT, Metagenomic Analysis Alignment Tool, which Michael can say something about because it's using clinical laboratories, isn't it?

It is indeed. And they screen both UDG treated, which removes the damaged DNA in non-UG treated libraries from their three. DNA samples that they were considered positive for the Salmonella enterica. They also... looked for a virulence plasmid that was a hallmark for this really nasty. And salmonella paratyphi RKS4594 harbors this virulence plasmid SPCB. which they included in their analysis capture design, because you're really looking for a signature that says, yes, indeed.

This organism had all the virulence characteristics that could result in the death of the poor soul who got the microbe. To extract that very specific information about what kind of bacteria they found required, as you said, a lot of computational power. And they found that with this new... that they developed, MALT, they were able to increase the speed 200-fold so that they could do this metagenomic analysis.

much more readily. So this technology is here to stay. And in fact, it's being used. There is a large number of samples available. which can be used for further study, which include organisms which are all over the place. TB, leprosybacillus. Yersinia pestis. Yersinia pestis, the agent of plague, is a favorite organism for studying ancient DNA because it went through a number of iterations, a number of changes.

There's something like 69 samples of old sinia pestis available for study. But I think the only Salmonella that they found... is the Salmonella enterica palatyphi C. So does this prove that Salmonella enterica cause the disease? And the answer is... Maybe. This is not I'll say to the author's credit, they worked hard to rule out other explanations. So, for example, they also collected soil from near where the graves had been, and they found none of this typhi DNA there.

And also the DNA had a fair amount of damage, which you might think, oh, that makes the experiment worse. But it actually validated that it was ancient DNA because other DNA that they got from... Soil, for example, wasn't so damaged. So they did what they could to make this as rigorous as possible. That's true. Haley, how do they look at some mummies?

Who were not in an epidemic area and then say there's no... That's right. They did. They did and they did not find the organism in there. Okay. Good. Yeah. Yeah. So it looks possible. I mean, is this the organism that caused this terrible plague? Well, maybe. It's possible that it does. Could you ever prove it, Elio? I think it's very difficult. You can't go back and reconstruct what happened. Well, if they understood where most of the migration was coming from, from Spain, for example.

Around that same period, maybe they could get some teeth, extract them, and see what kind of typhi was circulating, and then see how similar the two genomes were. Spaniards or Europeans and the genomes of the corpses in Mexico? Well, I think they did that in a way. Not so directly, but by... By showing you that this is Paratyphic and not something else, they found Paratyphic in Europe, but not much. They make reference to this in their discussion. They say, quoting,

origin for the coccalitzy disease has been proposed elsewhere. We believe that salmonella paratyphe C strains identified here were likely introduced from the old world. during the contact era, as evidenced by the existence of this human pathogen in Europe in 1200 CE. And so while this paper is... behind the nature paywall this paper was posted to bioarchive so you can sort of do a left-handed cheat

and see what they had to write. Because I don't think the bioarchive paper differs much from the one that's behind the paywall. Very good. Yeah, I think you're right. Anyhow, this is... Pretty much what I have to say, as I say, the subject of ancient DNA, by the way, it requires really very specialized labs because otherwise a little bit of contamination goes a long way to screwing up the whole study.

So people who do ancient DNA treat this like the most careful, requiring the most careful technology. Glove boxes all over the place. It can only be done carefully in a few places. And this is true for all ancient DNA, including that of... the Neanderthals. And the guy in Germany who I think is a Finn, Svante Pabo, is the man who really initiated this kind of study. So we have a very...

a nice possibility for studying ancient DNA. There's a newer paper that deals with this, and I don't think I'll go into that in detail because it doesn't say much more than what we know. So it's a combination. of very careful microbiology connected with the ability to use a tool in the computer, an alignment tool called MALT. which is really very good. Yeah, the review article you gave us, the past, present, and future of ancient bacterial DNA, is very good because...

It talks about all the examples of bacteria whose DNA have been found in ancient specimens. There are quite a few. And it's very interesting. I highly recommend it if you can get a hold of it. It's got a nice title, The Past, Present, and Future of Ancient Bacterial DNA. And this is really important, as some of you who have been following current science events know that NASA launched a probe.

that did a touch and go on an asteroid. And they're going to bring that specimen back to Earth. And one of the things I think they're going to look for is the evidence of whether or not this asteroid had life. And so they're going to have to use some of the same techniques to protect that precious sample to see whether or not there was indeed any DNA on that rock that's floating out in space.

And this technique, the malt technique that the authors applied, they also point out it has the advantage that it is not biased. It will just tell you, it will look at every DNA type. that's in their sample. You don't have to just interrogate it for a particular candidate and ask, is it there? So it's a way to get an unbiased profile. By the way. Vincent, do you think that the origin of the coronavirus may be studied by a similar argument that you can look for it in ancient DNA?

Well, coronavirus is an RNA virus, and that's a problem because we don't have very old RNA. It's not as stable as DNA, right? Yeah. So, yeah, we've thought of that, and it would— I think the oldest RNA is a few hundred years at the most. I see. But I would not be surprised if people are working on methods and might be able to do that. But the pieces would be very small, I think.

Because we really don't know where the COVID-19 virus comes from, right? Well, it's very similar to bat SARS-like coronaviruses that are circulating in China. Yeah, that's quite similar. So we're sure that it has its origin there somewhere, but the exact origin we don't know yet. And when this happened, when it really happened, we can only surmise...

by the appearance of cases, but that's not enough. Yeah. I mean, the earliest cases now in China are November, and then in December started to transmit human to human. So it could be that the first spillovers were... in November. But we don't know. Yeah. It's going to take a lot of environmental sampling, wildlife sampling to do that. And right now...

You know, relationships between the U.S. and China are not very good. So a lot of that has stopped. The U.S. has been funding some of it, and that has been stopped by the current administration. But hopefully we can resume again because I think it's an important question for sure. As is current contact tracing. Where did it transmit yesterday? Yes, the thing that we're most concerned about on our college campuses, as we get ready to send all our students back to their families.

that they hopefully won't kill grandma and grandpa. Yeah, it's a big problem. Really big problem. Anyway, thank you, Elio. That was good stuff.

Thank you. It's always nice to have some view into the past, right? Yes. Absolutely. It's not easy to get. A time machine. We used our time machine today. Time machine would be great. It connects to our current experience with the pandemic that we're living through now. All right. A couple of interesting emails. Megan writes, hello, I work in a private diagnostic lab that focuses on food production animals.

I was really excited to hear you discuss Erisipelothrix ruseopathiae. It is an interesting little microbe. It tends to be really easy to diagnose as it makes characteristic diamond-shaped lesions on the surface of porcine skin. It's a tough pathogen to isolate, though, as it takes two days to grow on BAP or PEA agar in a candle jar. Even then, the colonies are pinpoint.

It's odd to hear you discuss this as a zebra or unknown microbe, as it is something I am always on the lookout for. Food microbiologists are going to save our lives. They're going to save our lives by keeping our food supply safe. What is BAP and PEA agar, Michael? PEA is phenethyl alcohol agar. All right. BAP, I don't know what the B and A stand for. What are they good for? I know, I'm sorry. It's blood auger. What is this medium good for?

Phenethyl alcohol agar, it's selective and differential. It will actually kill off a lot of the normal flora affiliated with the skin. So, Michael, apparently it's blood auger. Okay. Sorry, go ahead. It just pulls out the organism because it likes a rich medium. Jober. Right. Hello again. Thank you very much for discussing the Deinococcus paper. Just a short comment on the enigmatic evolution of the Deinococaceae family. As you mentioned, they are highly resistant to gamma rays.

up to 15,000 G-rays, which is 3,000 more resistant than humans, and other oxidative stressors like desiccation and chemicals. Even though the radiation resistance in Daenococcus has attracted tremendous attention, it seems that they have adapted to stressors other than ionizing radiation. The reason is that the Earth has never experienced such a high flux of ionizing radiation.

What we know is that apart from radioactive environments, dinococcus cells are merely found in dry environments like deserts. It's been hypothesized that radio resistance trait is a byproduct of adaptation to desiccation, which introduces the same damages. to DNA double-stranded breaks. About my university, though, I am from the University of Waikato, but you pronounced it Wikato. Sorry. And in the end, my name is pronounced...

Jober. Or Jober. Sorry. What is this university? Waikato? I think it was in New Zealand. It's in New Zealand. It's in New Zealand. It is. And to give you an idea. It only takes about three to five grays to kill a fully grown human. And this microbe can withstand 15,000 grays. Well, it's because they miss it. It's too small. No, no, it hits it. It hits it. It just has that wicked fast repair mechanism because it has so many replication forks going.

All right. One more from Chow. Hi, my name is Chow. I'm a student at a community college in California. This is my first semester taking microbiology. I just listened to your podcast. Dirt is not simple. That was last one. I am still learning and understanding the fascinating world of microbes, and this particular talk caught my attention. In the talk, you spoke about and explained the difference between primary and secondary metabolism.

Is it more beneficial to do research on creating antibiotics that target the primary metabolism or the secondary metabolism? I've really enjoyed learning more about microbiology from your podcast channel. Thank you so much for your time. Nice question. It would depend. I would think if you want a broad spectrum antibiotic, then you might go for the primary metabolism.

If you want secondary metabolism because you know a particular pathogen does most of its damage with secondary metabolite. That would be my answer off the top of my head. How about you all? What do you think? I think that's a good strategy. And also, it's less likely that it will have a broad spectrum of activity if you isolate a secondary metabolite antibiotic.

And so it's less likely that you would develop resistance because the exchange of information would not necessarily do the microbe that acquired a resistance trait. from the organism that adapted to the drug, it wouldn't do it any good. So it would be deleted from its genome pretty quickly. So I would agree that this. going after alternative targets to primary metabolism are ideal. And in fact, that's what many of the drug companies are.

actively pursuings, you know, targeted antimicrobials to specific processes unique to the particular pathogen. So that we don't damage our normal flora, the microbiome. All right. That'll do it for TWIM 230. You can find the show notes at microbe.tv slash TWIM. If you want to send us a question or a comment, TWIM. TWIM at microbe.tv. If you like what we do, consider supporting us. You can go to microbe.tv slash contribute and join the legion of individuals.

who like what we do and donate a few dollars of their wealth every month. Michelle Swanson's over at the University of Michigan. Thank you, Michelle. Nice to be with you all again. Good to see you. Elio Schechter is at the blog called Small Things Considered. Thank you, Elio. My pleasure. It's a lot of fun. How would you say Small Things Considered in Italian?

Very good. I like that. All right. Michael Schmitz at the Medical University of South Carolina. Thank you, Michael. Thanks, everyone. Enjoyed it. And I'm Vincent Racaniello. You can find me at virology.blog. I'd like to thank the American Society for Microbiology for their support of TWIM and Ronald Jenkes. For the music, this episode of TWIM was edited by Ray Ortega. Thanks for listening, everyone. We'll see you next time on This Week in Microbiology.