Swords, cannibalism, poison: inside the world of killer microbes

Some microbe species have evolved to stab, bomb, cannibalize, or poison each other. Can we harness their weapons for good?

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:04Speaker 00

  In biological systems, microbe-on-microbe crimes are considered especially heinous. In the science world, the dedicated detectives who investigate these vicious attacks are members of an elite squad known as microbiologists. These are their stories.

• 0:23Flora Lichtman?

  Today, we are turning our attention to the serial killers right under your nose and perhaps inside of it. Microbes armed with weapons to eviscerate, assassinate, and detonate their victims. What turns a microbe murderous? How do they choose their victims? And can we harness their weapons for good? Today, we're talking with two biological detectives who've documented this microbe-on-microbe crime. Dr. Glenn D'Souza, an expert on bacterial butchers, aka cell-to-cell interactions, at Arizona State University, and Dr. Ben Larson, who just described a cannibalistic super-microbe in the Proceedings of the National

• 1:05Flora Lichtman?

  Academy of Sciences and studies how cells behave at Rensselaer Polytechnic Institute. Detectives, welcome to Science Friday.

• 1:12Speaker 02

  Thanks. I'm excited to be here.

• 1:14Speaker 03

  Hello. Glad to be here.

• 1:16Flora Lichtman?

  Should I picture you both in fedoras, smoking cigarettes, looking at a bulletin board with red string? Like, is that your day?

• 1:22Speaker 03

  Yeah, probably a cigar. That's not our lab roles.

• 1:27Speaker 02

  I think glued to the eyepiece of a microscope is probably the right picture for me.

• 1:32Flora Lichtman?

  Okay. Glenn, take me into this itty-bitty frightening world. I mean, do microbes have weapons?

• 1:42Speaker 03

  Yeah, and they have weapons, but it's not one weapon. There's like a million different ways to kill, right? So, you know, you can put them in two broad classes. You can have a weapon like a sword, you can keep on poking your neighbor. You can have these sort of teeny-weeny bombs you sort of unload into the environment and then kill whoever is out there, right? So that's sort of the two broad classes. It can get even more complicated. You can weaponize something else, right? You can have these viruses that you can sort of carry along with you, benign, and then suddenly decide, oh, you're deployed to attack a neighborhood. And so, yeah, there's a million different ways how bacteria can kill out there.

• 2:23Flora Lichtman?

  I mean, how murderous is this community? Do all bacteria have weapons?

• 2:28Speaker 03

  Yeah, I mean, that's like a difficult question. So at two levels, right? Because we do not know how many bacteria are in the first place, right? You know, we pretty much, I think, already describe about 5% of maybe most of all the bacterial life that is out there in nature. Okay, but of what we know, I think, I think their estimates, depending on which environment you look at, right? For instance, they've looked at the ocean and about 10% of all ocean microbes do at least have one weapon. Most have many, multiple weapons that they carry. But now, if you look at the plant root, for instance, I don't know what's happening there. That's like an entire sort of war zone. The plant root has like, I think, 30% of all microbes that carry at least one weapon.

• 3:11Flora Lichtman?

  Wait, plant roots have 30% of microbes that carry at least one weapon?

• 3:16Speaker 03

  Yeah, exactly. So if you look at the microbiome of plant roots, I mean, you can imagine the plant root is an extremely happy place. So microbes stay, right? So, you know, the plant keeps on throwing out stuff or teeny beeny pockets of sugar, candies, et cetera, that I think bacteria can go happily on. And if you're, if you're now in this amazing environment, you need to make sure you get it and your neighbor doesn't, right? So it makes sense to carry a lot of weapons out there.

• 3:41Flora Lichtman?

  Ben, they're fighting over territory. Are they fighting over other things?

• 3:45Speaker 02

  I mean, there can be fighting over territory, certainly, but a lot of the cells that I think about and study are fighting to get food. And so there can be, you know, arms races where they're battling one another or, you know, there are all sorts of fascinating predatory strategies that exist in the protest world that I think about. So the microbial eukaryotes.

• 4:06Flora Lichtman?

  Give me an example. Give me some of those examples.

• 4:09Speaker 02

  Okay, so the first one that comes to mind is one of my favorites. So there is this type of cell. It's a type of dinoflagellate. You might know about these things. Some of them are bioluminescent, or some of them can form these harmful blooms and become toxic. But there's a certain species where the cell actually has a structure. It's called an ocholoid, and it's basically an eye for the cell. So it's like a camera eye with a lens and a photo sensor.

• 4:34Flora Lichtman?

  Wait, a dinoflagellate has an eye?

• 4:37Speaker 02

  It has an eye. Okay, but not only does it have an eye, this cell also, this type of cell has a weapon. So it's not entirely clear how they're using the eye, but people have hypothesized that it's actually using that eye to track down prey. So it's light sensing, looking for the things that it feeds on. And then it has a little harpoon gun. So it's a structure, people call it a nematocyst. So that's also what people call the stinging cells of jellyfish. But in this case, it's actually a subcellular structure. So this pressurized harpoon gun in the cell that it uses to stab prey and get on a little tether and drag in and engulf. So that's one of the craziest ones that I know of.

• 5:11Flora Lichtman?

  That sounds very advanced.

• 5:13Speaker 02

  Absolutely. And I think that's one of the things that's most fascinating to me about all these protists, these microbial eukaryotes, is there's an incredible amount of complex cell structure and cell behavior associated, you know, with things like predation and navigating environments.

• 5:29Flora Lichtman?

  Glenn, does this reframe how we think about microorganisms?

• 5:33Speaker 03

  Yeah, I think so. I mean, as Ben mentioned, right, like getting food, no one has thought about that until now, right? Everyone thinks, oh, you have a weapon, you kill, you get territory happy. Or you have a contested resource, you displace your weaker competitor, you get access to your pot of gold, and you're sitting there happily. But, but the world is not a happy place, right? Like, so you will have these cycles of feast and famine, right? You'll, you might be on an amazing mutant patch, but suddenly you, there might be no nutrients out there. So where do you, how do you grow, right? You need to grow. And one idea people haven't thought about, and I think Ben kind of brought that up nicely, is every other cell is a pocket of food, except it's, it's in, it is amazingly encased in a way that no one else can get it, right?

• 6:15Flora Lichtman?

  Their peers are food. Their, like, peers are a snack.

• 6:19Speaker 03

  Exactly.

• 6:20Speaker 02

  So this, this gives me a great opportunity to, to, to jump in and talk about this cannibal that we, we mentioned here. So

• 6:27Flora Lichtman?

  Yes. Tell us about the super giant cannibal protist.

• 6:31Speaker 02

  Okay, I'll, I'll tell you about the super giant cannibal. So the, one of the cells that I study in the lab right now, or that the lab studies, is this single-celled organism, a ciliot, that can form these super giant cannibal cells. And they seem to do this Under conditions where small prey items become scarce. So what happens is they're in this growing population. The small bacteria that most of the cells are feeding on start to become scarce. And then this small subset of the population makes this choice to grow dramatically in size, rescale the cell structure and adopt these different behaviors and become cannibalistic. So instead of filter feeding on bacteria, they ractorially pounce on their conspecifics and devour them and eat them. And so there may be some, you know, competition for resource involved.

• 7:15Speaker 02

  We don't really know exactly what's driving the transition.

• 7:18Flora Lichtman?

  This is giving Marvel Universe vibes. Like this feels like the Hulk to me, you know, where you just, I mean, how much bigger are they getting?

• 7:25Speaker 02

  Yeah, so you know, the cell is about, the cannibals are three times as long as the, the normal filter feeding cells and cell volume, we haven't carefully characterized this, but you know, up to 10 times the, the volume of the normal cells. So they get a lot bigger. I mean, it's very, very clear under the microscope if you look at these.

• 7:43Flora Lichtman?

  Give us a little, just so we can picture it. What does it look like?

• 7:47Speaker 02

  Yeah, you can absolutely see this under the microscope. So what you see is mostly these normal sized cells and then these much, much larger cells next to them that are, they're densely packed with prey, with protein, you know, the, the body parts of the cells they've eaten and they run around like crazy. I think they will probably eat any big thing they can find to fit in their mouth. So they almost never stop moving, except after they've caught a prey item, then they'll stand still for a little while and ingest it.

• 8:15Flora Lichtman?

  Digest.

• 8:15Speaker 02

  They're very clear under the scope. Yeah.

• 8:17Flora Lichtman?

  Well, why are some lucky ones getting to blow up and eat their conspecifics, as you say?

• 8:24Speaker 02

  Sure, they're, they're sisters and cousins. We, we don't know. So this is something that we are actively trying to figure out. It is, it genuinely is a mystery because as far as we can tell, it seems to be this random subset of the population that's, that's making this choice. And we really don't know what they're specifically using to make that decision, what sort of underlying cell machinery makes that transition happen. But nevertheless, you know, it's, it's maintained at this relatively low level. Maybe it's risky decision. We don't really know. There's more that we don't know than that we do know at this point.

• 8:59Flora Lichtman?

  But that's interesting because it's only some of them, right?

• 9:02Speaker 02

  Yes.

• 9:02Flora Lichtman?

  Does that mean that some of them have different genes? Like, is it encoded on the DNA level? How does that work? That clones, some of them

• 9:14Speaker 02

  Yeah.

• 9:14Flora Lichtman?

  blow up and others don't?

• 9:17Speaker 02

  Yeah, so it seems unlikely that there's a genetic basis. Like you said, it's in this clonal population. So it's genuinely a mystery. I mean, it could have to do with RNA levels, with protein levels, with other physiological levels in the cell. And it may be very hard to find that, you know, what flips that switch. But one little piece of information that we do have is that, okay, so it's an extremely small subset. There's maybe, you know, only up to 5% of the population that we ever see in this cannibalistic form. It may be that more cells are sporadically trying to become these giants. So the first sign that the cannibals are going to show up is that basically the mouth of the cell gets much bigger.

• 9:59Speaker 02

  So before the cell body scales up, there's a bigger mouth that can maybe accommodate these large prey items. And I think that these cells that are sort of an intermediate phase, they're very bad at hunting. And so it ensures that, you know, there is this population density that's high enough that even a bad hunter can catch a prey item. And so it may be a very rare event that these big-mouthed but small cell bodies, cells can capture a prey item. And that's required to sort of flip the full transition to the supergiant state. And so that might be partly limiting the number. And so it may be that there's some, you know, regular probability of the cells trying to become cannibals and only a few really make it.

• 10:39Flora Lichtman?

  Are there places like where bacteria get along? Like, is my armpit actually like a beautiful bastion of peace?

• 10:46Speaker 03

  Yeah, I mean, so if you ask microbeauticologists, I think you'll create like, you know, they'll always fight with each other. Because there's a school of thought which says, oh, everyone likes everyone. I do not think so. I think there's these arms races everywhere, right? So essentially, I think another sort of arena. As you said, is is inside us, right? So there's a lot of competition that's happening in my gut right now, right? Because I just had breakfast, so maybe my microbiome is happy, it's getting food. But if I had an extremely fiber-heavy breakfast, so no simple sugars, no corn syrup, etc. Bacteria have to make an effort to digest that, right? That those are these huge blocks of carbohydrates. That's not like, that's not easy for bacteria to degrade, right? Inside me, there's a lot of bacteria that cannot do this.

• 11:32Speaker 03

  There's some bacteria that can do this, right? So the ones that can't do that, so you know, we call them scavengers or exploiters, essentially have to depend on someone else, the degraders, to do this. And if you don't want to do this in easier ways, well, I use my weapon. I wait for the degraders to do this, and then come and kill you and then eat you, right? So, so, yeah, so that happens.

• 11:52Flora Lichtman?

  Thanks for digesting my food for you, for me, now I'll eat you.

• 11:55Speaker 03

  Exactly, but I mean, the degraders might seem to be, you know, things are stacked against them. But no, they have an important card in this, right? They are the ones that can break down the food, they can control what goes out. So essentially, that happens in my gut. So I think it's happening everywhere. We see these systems in wastewater treatment plants, for instance. We see that in agricultural contexts, in the ocean.

• 12:18Speaker 03

  It's funny, we found a lot of signatures of warfare, microbial warfare, about 6,000 feet on the ocean floor, right? So that, and it might make more sense there, right? Because the nutrients there are extremely, extremely difficult to get. Oxygen is a problem, so yeah. So it's everywhere, except it might be at different levels in different places.

• 12:37Flora Lichtman?

  Ben, where did you find the super cannibal?

• 12:39Speaker 02

  So this was during fieldwork in the Caribbean on this island called Curacao. It's about 30 miles north of Venezuela. And so I had done some extensive sampling around the island, looking for interesting sites. But one place I had not sampled was the lab itself. And so these supergiants actually came from a filter system on these water tanks that pump in water from the, from the sea and fill up these tables that people keep animals in. And there's this disgusting filter and scraped that. And lo and behold, I found some cannibals on that filter sample.

• 13:11Flora Lichtman?

  That seems right.

• 13:12Speaker 02

  So that's where they came.

• 13:14Flora Lichtman?

  A dirty filter seems like exactly where I would find a villainous beast, you know?

• 13:19Speaker 02

  Yeah, exactly. And for any, you know, amateur, uh, microbe hunters out there, I would highly recommend fish tank filters as a great place to find interesting, uh, cells and perhaps violent cells as well.

• 13:34Flora Lichtman?

  We have to take a quick break, but coming up, can we harness these microbial murder weapons for good? Stick around.

• 13:48Speaker 04

  And from the Alfred P. Sloan Foundation, working to enhance public understanding of science, technology, and economics in the modern world.

• 14:02Flora Lichtman?

  Okay, Glenn, we've been talking about these micro murder weapons, microbial warfare. Can we harness them?

• 14:10Speaker 03

  Yeah, I mean, definitely we can, right? So one of these systems that I keep on saying is a spear gun, right? What the spear gun does is delivers toxins into another cell. But we can, you know, essentially, these are assassins. What if you train an assassin? Or what if you train a hitman to find or to remove things you don't like, right? For instance, historically, we've used antibiotics to get rid of undesirable bugs from our systems, except antibiotics are indiscriminate. They might just kill everyone. They might kill the good ones, right? We know that these killing bacteria are extremely specific in who they like to target or what kind of bugs they like to target, at least in many cases. What if we can learn

• 14:51Speaker 03

  more of this system and then engineer living antibiotics? Essentially, you can load any drug on these killing systems and then create a assassin cell that you introduce in your microbiome and say, okay, go and find, um, the undesirable one and displace it off, right? So I think that's, that's, that's an important area of inquiry in at least my field.

• 15:14Flora Lichtman?

  I mean, are there specific disease candidates that you think this would work for?

• 15:17Speaker 03

  Yeah, so typhoid, for instance, or cholera, right? So the bugs we study are essentially the causative agent of cholera. And one of the ways cholera can survive in our bodies, or even salmonella can breach our bodies, or salmonella is the causative agent of typhoid, can breach our bodies is one of these killing systems, right? So if you study the systems in more detail, or essentially what shields might work against the system, then essentially you can create a sort of a barrier for salmonella to not enter my epithelial cells in my intestine, or cholera to not infect my gastric layer, right? So, so, so, yeah, if you could target those bacteria, I think that would be one. Wounds, for instance, right?

• 16:00Speaker 03

  Staph aureus creates these pus-like wounds in burn patients. We don't have a way to cure, but we have antibiotics, but staph aureus essentially becomes resistant to any antibiotic out there. So you can create living killers, and you can introduce them. Again, a long shot, but it's possible.

• 16:21Flora Lichtman?

  I mean, Glenn, you study a lot of bacterial species in the ocean. That feels like a very different ecosystem from the body. Is there anything transferable there?

• 16:31Speaker 03

  I, I think of the ocean as a giant human gut.

• 16:37Flora Lichtman?

  Really?

• 16:37Speaker 03

  Yeah, I think the reason we study the ocean is, I mean, yeah, we want to know more about the ocean, but I think the ocean is a simpler place to study, but you can have principles that are translatable, right? So, for instance, I eat a lot of food, the microbiome digests it, and that's broken down and given to the cells in my body. In the ocean, algae produce a lot of food, bacteria now take all this food, break it down, give it to our organisms. So essentially, the same processes happen in two different places, right? So I think we can learn a lot of things that are immediately transferable, right? How do bacteria break these things down? How do bacteria kill and get nutrients out? For instance, the stuff we do, like, you know, killing to get nutrients out, that, that happens in my gut, that happens in the ocean.

• 17:19Flora Lichtman?

  You know, hearing you all talk about this. I think it challenges our assumptions of sort of the decision making that microorganisms are capable of, and maybe that's not even the right term. But how do you think about this?

• 17:34Speaker 02

  Well, OK, so I think a lot about cell decision making in a few different ways. So, you know, one thing I will add that may even further challenge basic assumptions about how cells work is that there are some ciliates that have a well documented capacity to learn. So there is one, for example, called stentor, and this is a cell. You poke it and it'll contract into a little ball. And it turns out, you keep poking that cell and it will eventually learn to ignore you. But it's not that it's just tired. You know, if you give it a different aversive cue, it'll still be able to contract. Or if you poke it harder, it'll actually contract. And so it's learned something specific about the way that you're poking it. And there are other cells that can solve really complicated geometry problems.

• 18:15Speaker 02

  You know, there's this, you know, famous ability of this slime mold called fecerum to find the shortest path connecting a bunch of different pieces of food. And so, you know, when I look out in the world, I see all this, you know, complex decision making that these cells are capable of. And I think about it on these behavioral timescales. So it's stuff that you can just directly observe under the microscope. And so I think, you know, people are becoming increasingly interested in this idea, although it's not a new idea at all. You know, as some of the earliest observations of these protists of microbes were describing these kinds of complex behaviors that I've been talking about. And so there's actually a long history of people even thinking about cell psychology. You know, we now know that cells don't have a brain.

• 19:00Speaker 02

  They are indeed single cells. But nevertheless, they have this rich, diverse repertoire of behaviors and ability to make decisions that help them navigate diverse environments. And so there's just so much out there to learn.

• 19:12Speaker 03

  Yeah, I mean, I agree. I think, you know, historically, if you think, you know, if you type microbiologist and find an image, you'll be people staring at a petri dish, right? But I mean, the earliest microbiologists were not like that. Like, they would, as Ben said, look at the microscope, right? And I think looking at, looking at cells as opposed to petri dishes can get you so many places, right? For instance, We know talked about stentor, but bacteria can also learn, right? Like, they don't have a brain, or I don't think they have a brain. But essentially, if I subject some, you know, E. coli cells to, say, a salt stress, so give them, you know, they like less salt, but if I subject them to salt stress, and then look at the progeny, and then the progeny of the progeny, there are signatures out there that they remember those stress, right?

• 19:57Speaker 03

  So the progeny can take salt stress much better than, say, cells that haven't seen salt stress at all, right? So they have some sort of memory encoded, not memories like we have, but some sort of memory encoded in there, right? So I think cells remember, or at least not on these very long timescales, but on short timescales, right? And a short timescale for a cell is at least three generations for a human, right? So cells do remember that, right? So I think there's a lot of things we do not know. And I think that's, I think, the next frontier, trying to understand why do you decide based on where you are, based on who's around you, and based on what genes do you carry?

• 20:37Flora Lichtman?

  So fascinating. Dr. Glenn D'Souza is an assistant professor and microbial ecologist at Arizona State University, and Dr. Ben Larson is an assistant professor and cell biologist at Rensselaer Polytechnic Institute. Thank you both for taking time to talk to me today.

• 20:51Speaker 02

  Yeah, thank you. This was so much fun.

• 20:53Speaker 03

  Yeah, this is very fun.

• 20:55Flora Lichtman?

  This episode was produced by Rasha Aridi. And if we murder your boredom, annihilate your ennui. What do you think, guys? Who are you going with this? Please rate and review us right here in this app. It helps us out so, so much. We'll catch you next time. I'm Flora Lichtman.