Our Universe Revealed, Part 9: The Secret Social Life of Bacteria

Episode Topic: The Secret Social Life of Bacteria 

Have you ever wondered how bacteria communicate, cooperate, and even compete in ways that impact our health, environment, and beyond? More than just making us sick, bacteria form alliances, wage wars, and orchestrate remarkable feats on a scale so small, yet so influential. In this talk Maggie Fink '24 Ph.D., will unravel some of the microbial mysteries that shape our lives, and help us gain a new appreciation for the invisible hidden dramas unfolding all around us.

Featured Speakers:

- Maggie Fink '24 Ph.D., Adjunct Professor, Indiana University South Bend 

Read this episode's recap over on the University of Notre Dame's open online learning community platform, ThinkND: https://go.nd.edu/39dd0b.

This podcast is a part of the ThinkND Series titled Our Universe Revealed. 

Thanks for listening! The ThinkND Podcast is brought to you by ThinkND, the University of Notre Dame's online learning community. We connect you with videos, podcasts, articles, courses, and other resources to inspire minds and spark conversations on topics that matter to you — everything from faith and politics, to science, technology, and your career.

• Learn more about ThinkND and register for upcoming live events at think.nd.edu.
• Join our LinkedIn community for updates, episode clips, and more.

Transcript

Welcome to the Series

1 0:00

Happy New Year. my name is, DevMar. I'm a professor of ecology at Indiana University South Bend, and I'd like to welcome you to the Our University Reveal Lecture Series. Um, this is the first of our 2024 talks. the series includes, talks in the sciences and the arts, so steam for everyone. And tonight, we're gonna be kind of blending those two, both science and art. We feature current research and creative work that's being done in our region, and it's an opportunity to be curious about ourselves, our universe, and the earth. this is a partnership between IU South Bend, the University of Notre Dame, and the St. Joseph County Public Library. Tonight is my pleasure to introduce Maggie Fink. Maggie received her bachelor's degree in biochemistry from Indiana University South Bend. And she's an award-winning scientist, poet, and illustrator. Maggie has developed a blog called Folding Moonlight that uses the visual arts and storytelling to illustrate biochemical concepts relating to protein structure. Maggie and Shahir Risk have co-authored an upcoming book, What Color is North, um, that explores the intersections of science and art. In 2020, Maggie received a National Science Foundation graduate research fellowship. This is a highly competitive and prestigious, uh, fellowship that o- recognizes the top graduate students in the country. Maggie's a PhD student and professor Joshua Strautz lab at University of Notre Dame, and she's studying different species of bacteria to see how they can communicate, cooperate and compete under different conditions. This work contributes to our understanding of the underlying mechanisms by which bacterial crosstalk affects their behavior in the environment and during infections. So without further ado, I'm gonna turn it over to Maggie to take us into a really wacky world.

Speaker 2 2:08

Thank you so much, Dr. Marr, for that introduction. Um, I hope my mic is working okay. I didn't test it beforehand. Okay, awesome. Um, this is super special for me to be here this evening. I grew up here in South Bend, and I came to this library growing up, so being able to do my PhD work here at Notre Dame still, and now come and give a talk at this library is very special. As you noticed, you were handed and instructed to take some paper and some coloring materials. I know this is a science talk. If you do not have it, please feel free to get up and walk up here and grab it. I will not care. I teach yoga, so I'm used to bodies moving around while I'm talking. No problem at all. And if you're inspired to get a different color in the middle of the talk, please feel free to get up and move around as well. As Dr. Marr mentioned, I'm interested in science and art, and my collaborator, Shahir, is here as well, and we do a lot of art and science and explore how those two actually intersect. And so you're part of an experiment for me tonight. To have participants in a science talk actually be making art during the talk. So whatever you're inspired to draw or doodle, whether it's related to anything I'm telling you or not, feel free to be creative and inspired and keep it to yourself if you're embarrassed or show the world. but just to see what it's like to use both sides of your brain, if you will, make some art and learn some science. so again, feel free to move if you feel like you need a different color. You will not bother me at all.

Bacteria Are Social

Speaker 2 3:42

So I'm gonna talk to you guys tonight about bacteria, which might be a little confusing because I did get my undergrad degree in biochemistry. I very much did not want to work with living things. They kind of scared me a little bit. I found them not very interesting. Sorry, Dr. Chen, my microbiology teacher at IUSB who's here. Um, I took her class. It just didn't quite inspire me at that time. And then I went to Notre Dame and I had to do a rotation in a biology lab, so I landed myself in Dr. Schrout's lab, where he studies bacterial behavior, which turns out is much more interesting than just thinking about bacteria in terms of an infection. And it turns out also that bacteria are incredibly social. They like to interact with each other and they have very complex lives, so I'm here to tell you a little bit about that and how my research and the research in the Shroud lab investigates that as well. But I always start off every talk, telling the audience about one of, I think, some, one of the coolest scientists, his name was Anthony Van Luven Hawk, and he lived about 400 years ago in the 1600s, and he invented some of the first microscopes and talked about some of the first bacteria that humans were able to actually observe. You can see some of his illustrations that he did over here, again, science and art. he took some dental plaque from his teeth, scraped it off and put it under a microscope, drew them and described them this way. First, he described what was on his teeth as a little white matter, which is as thick as if it tort batter. I think we can all relate to that in the mornings. And he said, "I then most always saw with great wonder that in the said matter, there were many very little living animolecules, very pridily and moving, where over, the other animolecules were in such enormous numbers that all the water seemed to be alive." And I love his description of what he saw under the microscope. At that time, they didn't know anything about bacteria, so he called them antimolecules. And today, we don't know how he even made these microscopes. Nobody's been able to replicate it, so I think this guy is kind of one of the coolest microbiologists to ever live. He kept his secrets very safe. But today, we have a lot more tools to be able to look at bacteria and to understand them and to characterize them. And here we see this microscopy image of, again, some dental plaque that was taken off somebody's teeth, and this is under a much more high-powered microscope, and we can actually visualize different colors associated with the bacteria that we can give them. And in this dental plaque, each of these colors represents a different species of bacteria. So in our mouth, are all these bacteria, they're very complex, they're very interwoven, and now we can understand a lot more about how they interact with each other, with our own bodies, and with the environment around them, and how social they actually are. And we should probably start by defining what a bacteria is. It's never good to assume the audience knows. So bacteria are single cell organisms, right? Everything they need is in one cell, and we kind of think of them as just moving around isolated But imagine, if you will, in this, if this video was playing, a bunch of little cells just kind of floating around, willy-nilly. There's no kind of coordination or movement together, which is typically how I always thought about bacteria, that they just kind of do their own thing because they're single cell organisms. But we also know that bacteria are everywhere. We already saw that they are in your mouth, they're on your skin, they're in your bodies, they're probably on this floor, they're in the dirt outside, from the highest mountain to the deepest ocean, we'll probably find some bacteria living there. And if you can tell by the sound of my voice, bacteria also cause infections, which is something we're all familiar with in one way or another. Little kids always getting ear infections. I currently have a sinus infection, so we do know that they can be problematic. But for the most part, bacteria are incredibly important for every ecosystem, every organism that lives on this planet. Every animal has some bacteria living with them that helps them survive. We have bacteria in our bodies to help us survive. So yes, they can make us sick, but they're important, and if we didn't have them, we would really notice the effect. And lastly, bacteria are actually very complex. I'm doing a whole PhD on one type of bacterium, doing one specific thing, eating one specific type of food, and that can be a whole PHD thesis and not even scratch the surface. And if we think just about the bacteria that are in us and on us, and put it into perspective about how important these bacteria are, if we compare the amount of microbial cells that are in and on us, to how many cells are our own human cells, we can see a huge difference. There's about a hundred trillion bacterial cells in and on us right now, and we only have about 30 trillion human cells, so all of you are actually mostly bacteria here today. And we can think about that in terms of DNA as well. If we think about the actual number of genes that we have in our bodies, we have about 23,000 genes. Bacteria that are on our bodies, if we take all those cells and figure out how many genes they all have, it's about two million. So 99% of the genetic information in and on you tonight is bacterial. So again, most of you are just a clump of bacteria cells right now and a little bit of human. So if we have this many microbial cells and we have this much genetic information going on, there must exist some type of community, some type of collective behavior that the bacteria have to be engaging with, to be able to keep everything in balance and equilibrium so that one doesn't outgrow another and totally set our bodies off of whack. There has to be some type of social dynamics involved in these bacteria. And I'm not a sociologist, never taken a sociology class, but I have an idea of what communities look right, look like, and here's our beautiful city of South Bend. We know that there's some things that we can kind of always find in some type of community. And those include a few things I've put together here that I also mentioned in my research talks when I'm talking about my research and bacterial communities. We have neighbors. I have my neighbor Carl and his three-legged dog, Maggie, that I hear about every day. We have places we can go and gather. We're here in a structure we have our homes we'll go back to, and we also have to be able to communicate. We get the newspaper, we have social media, we have the gossipy neighbors. There's always something going on for us to be able to communicate within our community. And these last two we have eat, we need to have resources available to fuel our bodies, to fuel our cities, and we need the ability to move around in these spaces as well. And it turns out that bacterial communities exhibit all of these same things in one way or another. And here's a picture I took on our microscope in our lab. Maybe you can see each of these little dots is a bacteria. This is pseudomonas originosa, the organism, the eye study. So you can see they're all grouped together. They're all collectively. If this were a movie, you could see them all moving together at the same time. So these bacterial communities do mimic a lot of what we would define a community in as humans. So this has led to this idea of sociomicrobiology, which in the past 20 years has been pretty widely accepted. Oh, let's see if this will play. We're having some technical difficulties, so I don't know if all these videos will play, but if it were playing again, you'd see these bacteria all moving around together collectively. One group will join another and then the other group will break off. So it's not just one cell, it's not just one of these moving around by itself, they're actually moving as an entire collective. And so this idea of sociomicrobiology has been widely accepted now in the past 20 years, because we know bacteria are not these isolated things, these lone wolves that exist out in the environment. They're actually quite dynamic, responsive to their environment and behave and very distinct and intricate group behaviors. Excuse me. So if these do in fact exist in communities within these kind of parameters that I've laid out, can we actually observe them through a more sociological lens and characterize behavior rather than individual, actions by a single cell? And one of the first bacterium that was widely accepted to be considered a social bacteria that has group behaviors is this group of bacteria called mixobacteria. And this is another organism that the Shrout Lab at Notre Dame studies. This bacterium is found in soil. It will decompose a lot of organic material, and one of its defining characteristics, which you can see here in this image from this species, is it forms these fruiting bodies. So all of this tan is just a bunch of bacterial cells, and these orange sections are also incl- have also bacterial cells inside of them, and they've encapsulated themselves, to survive a stressful environment. And it looks very similar to what we see with different fungi that form these fruiting bodies in response to the environment as a form of self-preservation. So these individual cells are able to respond to the environment in a way that they begin to completely change how they look, behave, and aggregate together. So this was pretty widely accepted to be, okay, we have just a couple of these different types of bacterium that will behave this way, but everything else, is just an individual bacteria. And the other thing these bacterias can do, which again, is that they're able to have this group predatory behavior. So what you can't see at this point in the video, this whole thing here was just plain, none of these ribbles, and that was an E. Coli colony. And over here, we had this mixicoccus bacteria, myxofocus zanthus. It started off as just this small circle, and it started to spread across the plate, completely covering the C. Coli colony, and you can see these cells are lined up in a very, ordered pattern as they move across the C. Coli to take it over and kill it. So they have this predatory behavior that results in very synchronized movement, and to be able to do that, you have to be able to communicate and have some type of social behavior as a bacterium. Now, about 20, 30 years into some of these questions about bacterial behavior, it's pretty widely accepted that mixobacteria are not the only bacteria that do that, that most bacteria, if not all, do engage in group behaviors and interact with each other in ways that multicellular organisms do. And we can see here some more examples of these mixobacteria forming these fruiting bodies. There's a wide range of structures that we see coming from these bacterium that are very much reminiscent of fungi, and so there is some question there of maybe this is the branching point from bacterium into more multicellular organisms. That question still is not known, but I hope you can appreciate that we go from single bacteria to these very intricate 3D structures made up of many different bacterial cells. So, excuse me, those bacteria.

Biofilms Bacterial Architecture

Speaker 2 15:58

I wanna talk just about two of these ideas of community features in bacteria. A lot of my research covers all of these and we'll kind of weave them in and out, but the two I wanna focus on tonight are this idea of gathering how bacteria have, the ability to create homes for themselves that are very complex and their ability to talk and communicate with one ano- one another. And here on this Petri dish, you can see, this is actually taken from my son's bearded dragon lizard. Uh, these are all the bacteria that he found on them during the science fair project last year, so it's not just us, it's also lizards that are friends with bacteria. So we're gonna start by talking about gathering and this idea of structures and architecture that bacteria need to survive as a group. And these are called biofilms, and you can see this one here. This is from a bacterium called bacillus subtles, and this is just growing on a Petri dish on a flat surface, and it's grown out, and it's formed these incredibly intricate, 3D patterns that you can't really appreciate in just a 2D image, but it's not just a clump of cells, there's clearly some design and in- intention behind creating this, architecture. And biofilms are actually how the majority of bacteria exist in the wild. About 90% of bacteria that we'll find live in this biofilm state, and these two pictures on this far side here from Yellowstone National Park that I took several years ago with these really pretty colors, those are bacteria living in biofilms in some of these, um, hot springs, and we also can find biofilms on the bottoms of ships. We see this a lot in marine environments, these biofilms forming, and they can be problematic for the function of a lot of this equipment. but again, if you go out into the river and the rocks, you'll see all this slimy, slippery stuff, and that's probably gonna be a biofilm with a lot of bacteria living in it. We also will find biofilms on our teeth, like we've already talked about. We'll find them in our bathtubs. I decided Yellowstone was prettier than a gross bathtub to show you guys, but I'm sure we've all encountered some gross things growing in our bathtubs, and we also see this a lot in hospital equipment. If we want to think about it from a human health perspective, biofilms are very problematic when we're thinking about, implants or catheters and things like that. So basically how these biofilms form is there might be some free floating bacteria in the environment, and they're gonna come in contact with some type of surface. It could be a catheter, it could be a rock, or your morning breath teeth, and it'll decide to attach to that surface. Bacteria do this in a wide, uh, range of ways that is totally beyond the scope of this talk, because there's so many different ways that bacteria can begin this, process of starting a biofilm, but essentially, they'll realize that they're on a surface, and they'll anchor down and say, "We're staying right here." And they'll kind of begin to grow, and they'll start making this really goopy salami stuff, and that's what you feel on your teeth, or you slip on a rock on the river, and it grows and grows, and these bacterial cells are encased in this gunk, and that becomes a biofilm. And eventually, some of these bacteria might be released and break free, and go on to settle onto a different surface, us ensuring the survival of the whole community as they go on and create more and more. And we can actually take really cool microscopy images of the inside of some of these biofilms. Up here at the top, again, is my favorite pseudomonas originosa, those long rod shaped bacteria, and you can kind of see there's a bunch of gunk coating these cells, just a lot of goopy stuff that they're secreting out, outside of themselves, and that's gonna be a part of that biofilm. And then here, we have facilitus, which may be a little bit harder to see some of these cells in here, but they're wrapped up entirely in some web of all kinds of different things. And you can even see inside this biofilm that there's tunnels and channels for the bacteria to have water flow through. So they're not just, again, these clumps of cells that aren't ordered, there is a really intricate design to the insides of these biofilms. And what that gunk is made up of mostly is sugars, different types of long carbohydrates, real sticky things. There's also a lot of DNA present in these biofilms, and then we have proteins as well that can help do lots of different, chemical jobs inside the biofilm. These can be very thick and very difficult to remove. That's why we brush our teeth in the morning and scrub our bathtubs, and then even in some of these marine environments, having to physically go in and scrape off some of these biofilms that have formed. But from the bacteria perspective, this can be very protective from them, and it helps them stay safe in some of these really harsh environments. In the lab, we can grow biofilms in several different ways, and since our lab studies a lot of biofilms, we're able to do this, and it's my favorite part of my job, is being able to take some of these microscopy images. The first one is one I took not too long ago. This is just growing a biofilm on a Petri dish. So we fill it up with auger that's pretty solid, so it mimics a surface. We drop some bacteria on there, they adhere to that agar surface, and they start to spread out and form a pretty, even shaped biofilm. And here, we actually have two different species of bacteria in different colors, so you can see one has spread out this way in the blue, the other one's kind of inside and has formed some more intricate structures. And that's a pretty simple way to grow a biofilm. You can also grow them on implants in the lab, so this is an image of a dental implant that has some staph aureus growing on it here, and we can see that it looks very different than what a Petri dish, biofilm might look like. In this last one, um, these are grown and what are called flow cells, and essentially you stick bacteria onto a glass microscope slip, and then you're having water and nutrients flow over it, like a river, to mimic some of the factors that might be at play in the environment, that might affect how biofilm forms. And if you're thinking of maybe like a catheter, again, going back to human health, when urine comes out, there's gonna be some physical force of liquid flowing over that biofilm, and that might change how it looks and how the bacteria behave. So we can look at biofilms in a lot of different ways in the lab, trying to replicate the environment that the bacteria are naturally gonna be found in. And for the talk, I'm gonna really focus and show you guys stuff with these colony biofilms just because they look the prettiest, and they're kind of the easiest to explain and understand as we begin to, add more complexity into biofilm social life. So here you can see a time lapse video of one of these biofilm colonies forming. So they've dropped some cells onto the surface and you can see at the very beginning, it's pretty much the same throughout. You start to see a little bit of change in the structure, but as it grows and spreads, there's really distinct regions within this biofilm structure that we can characterize. So in the middle, it looks different. There's this ring kind of in the whole center of it, and as you get out to the edge, you lose some of these 3D structures as well. So I love this image, this again, is pseudomonaserginosa, which is one of the primary bacterium that is used to study these social behaviors, um, because it does some really cool things. So that's why I like it and why we study it. So let this play one more time just so you can appreciate how, intricate these are. Again, not just a random assortment of cells, there is a lot of order to this. And if we think about biofilms and we kind of project up to the microscopic and see what kind of similarities there are, there's quite a few, especially if you're, before you start to add some more complex layers. And even thinking about, I love this one, urban growth. So when we're thinking about how cities grow and expand, there's usually a central place that starts, and then as the city grows, people come, there's distinct regions in the city. There might be the shopping district, there's the business district, there's suburban areas, there's apartment living, and it's pretty concentric rings that come out of that city growth. And we see that in this biofilm here, there's these really distinct regions that form as the biofilm grows. We see this in tree trunk growth, which we might be a little bit more familiar with as a tree grows in these concentric rings. It really starts to kind of look like a biofilm does as well. And even, um, our own bones in, in our bodies, they have the same pattern of concentric ring growth. So there is something about bacteria growing this way that mimics how things on the macroscopic level grow as well, which allows us to kind of approach it from a more sociological point of view. And within these regions of a biofilm, we have really distinct bacteria doing things that might not make quite sense in the next slide, we'll go over it a little bit more, but not all the bacteria are behaving the same way in each of these sections. So here's another biofilm from the bacteria and bacilus, another pretty commonly studied one when we're thinking about biofilms because they make these really pretty structures. So when we start growing a biofilm and we add the bacteria to the Petri dish, all of those bacteria are genetically identical. They're all clonal, so there shouldn't be any differences between them. They have the same genetic information and they're doing the same thing. But as the bi- the biofilm begins to grow and expand, we see different regions of where the bacteria are using different genes. So we can see if a gene is turned on or turned off, we can see what kind of proteins it's making, what kind of sugars it might be eating, and in every single region of these biofilms, we're gonna be able to see bacteria doing something different, even though they should all be genetically identical. So they're able to begin to differentiate, which again is kind of a hallmark of a multicellular organism, where each of the cells in our bodies are doing something very different, even though they all have the same genetic information. So practically, if we just kind of divvy it up with cells in the middle and cells on the outside, we can see that the cells at the edge are gonna be exposed to more environmental hazards because they're the ones that are actually moving outwards, going into the environment, they might encounter one of those predatory bacteria, they might encounter some nutrient starvation, so they're gonna need to have access to different types of genes to be able to encounter those. While the bacteria on the inside aren't gonna really need to worry about that, they're actually gonna be under more starvation, they're gonna be limited in oxygen, so they're gonna have a different set of tool set that they're using. So even though that these are genetically identical, as far as we c- you know, theoretically they should be, they're gonna start behaving very differently depending on their location in the biofilm. So one last cool picture of a pseudomonas biofilm, again, seeing these really intricate 3D structures form, why would they wanna do this? 'Cause it takes a lot of resources and a lot of energy to build a biofilm like this, but just like in human, there is strength in numbers. So the more of you that are around coordinating your behavior, the more likely you're gonna be able to survive and you're gonna be able to withstand some of these environmental stressors. In the lab, those stressors don't really exist. We give the bacteria as much food as they want because we want them to grow quickly so we can go home for dinner, but in the real world, that kind of thing is not gonna happen, so they have to adapt to whatever environment that they're in. This also allows for sharing common goods, so maybe only some of the bacteria are making products that will benefit the whole group, and that allows the other bacteria to spend their energy doing something else while the other bacteria makes some, common goods for the whole group. And those complex structures allow for more adaptable behaviors in the environment. So this is kind of how bacteria live in the real world. It's not always gonna look like this pretty, colony, but the idea is the same that, that they're coordinating the building of a house for themselves, essentially. But that means that they might need to, to communicate with each other. You can't just have one person going rogue. You need to kind of coordinate and communicate who's doing what and, so that you can survive out in the wild. So the last thing we'll talk about here is how bacteria talk, and this is actually where I kind of got interested in bacteria a little bit more. And you might be wondering now why there's a picture of a squid on the screen instead of a bacteria. I wondered the same thing when I was taking a microbiology class in grad school several years ago. I was like, Why is there squid? We're here to learn about bacteria. "This is the Hawaiian bobtail squid, super cute, like very little, and this is really how researchers figured out that bacteria actually communicate with each other and, happens right here in this little light organ on the bottom of the bobtail squid. And again, my video's not playing. There'd be a very cute video of a bobtail squid digging around in the sand. but for now, uh, I will just kind of walk you through why this squid is important for bacteria. So a bacterium called vibrio fisherie actually will colonize this light organ in the bobtail squid, this thing that glows at night. So all these bacteria will come and when the moon comes out, they'll start to all glow at the same time. So you can see them in the dark, you can kind of see it. This is a Petri dish with some of these bacteria streaked out. You can see that they're blue, they're glowing in the dark, super fun to play with. Um, my kids love it when I bring some of these home. But then in the morning, the squid stops glowing. So how are the bacteria able to decide? This is the time to start glowing because that, that light produces some counter illumination for the bobtail squid and protects it from predators. It basically gets rid of its shadow as the moon is shining down on it. So the predators can't see that there's a squid swimming around. And then when the sun comes up, it's not an issue, so the bacteria stop glowing. So what happens is the squid actually spits out a bunch of these vibrio fisherie, gets rid of a lot of them. So there's only a few left inside its body. So during the day, these bacteria are growing and growing and growing. And then finally, when the moon comes out, they start glowing. So, but the researchers who did this thought maybe it has something to do with bacterial population and that's how they're communicating and it turns out that is correct.

Chemical Languages and Signals

Speaker 2 31:06

So essentially what the researchers discovered is that bacteria are communicating through a chemical language. So we have a single bacteria here and it's putting out this molecule into the ether, which you can kind of see depicted with that little red dot. Just sending it out there. As the more bacteria come as they grow and divide, there's more of this molecule being made. More of it out there, bacteria is starting to get a sense that this molecule is around. And then eventually, once they reach a certain threshold, the bacteria say, "Okay, there's enough of us here. We have reached a quorum. Now we will begin to glow." And so they can synchronize this group behavior with the ability to sense who is around them using this molecule. Basically they're saying, "I'm here, I'm here. Are you here? I'm here." And when enough of them get around, they're able to turn on everything needed to start glowing. And if we kind of look at this, go into the molecular biology of this a little bit, which I'm not a molecular biologist, but if we look at it just a little bit closer, how this actually works is again, these molecules are being sent out, these purple pentagons here. And when enough of them show up, this protein here will actually be able to bind onto one of those molecules. It'll grab it when there's enough of them around. They'll be like, "Okay, I've got one. That means there's enough of us around." And it'll come down to the DNA of the bacteria and just sit right here, right in front of all the information needed to make the proteins and the equipment to start glowing. And it'll say, "Hey, come. I'm ready for you guys to start making this protein and it'll recruit all of the equipment needed to make these." But it won't do that until it senses that there's enough of these molecules around. So if they're not around, none of this genetic information is being used. Okay? I know molecular biology, it's not my favorite, but I hope this gives you kind of a basic idea that it's linking the ability to sense the presence of other bacteria to turning on genes at the same time. And it's not just bioluminescence that this happens in. Many bacteria use quorum sensing to, coordinate the group behaviors. We can see here we're looking through into a biofilm with all these different bacteria. They use quorum sensing to, to build that biofilm. They also use quorum sensing to move together. I took this video in our lab, this is pseudomonas. It exhibits this type of motility called swarming when they'll just spread across the plate, forming these really cool tendrils, and then come back to center. And it does that through communicating using quorum sensing. And this other thing that it does, again, kind of everyone always is interested in human health. it, it uses quorum sensing to sync up attacking, uh, a host. So this molecule that's blue and green here, you can see that's associated with an infection. So they want to be able to make that molecule when they're actually ready to infect a host, not just randomly have each bacteria doing it on their own, because that wouldn't be very effective. So they use this chemical language to say, "All right, it's time. Let's go. And again, these are all pseudomonas, another really common bacterium used to study this communication. So then this quorum sensing also lets bacteria, figure out self from non-self. How do I know if it's a bacteria that's family or friend or if it's something else that I don't want to talk to? And quorum sensing allows bacteria to do that as well. Here's a bunch of chemistry. so I'm not going to quiz you on this, but basically every single bacterium will make its own molecule that will only be recognized by a bacteria of that same species. So here in gram-negative bacteria, which is just one way we can kind of group a certain type of bacteria together, we have all these different molecules, they're called acyl-homosearing lactones, AHLs, and they all look kind of similar. So they're in the same family, but each one's a little bit different, so that only one bacteria species will be able to recognize it and not others. And we can see this is true too for gram-positive bacteria, another type of grouping. They make a different type of molecule that are a little bit more complex, but the theory is still the same that these molecules are specific to the species of bacteria that it wants to communicate with. So that help its recognize self versus non-self, which is very important when you're spending so much energy and resources into coordinating these group, group behaviors. But bacteria are also multilingual. They can communicate with bacteria of other species. They can also communicate with, eukaryotes, so humans, plants, fungi, and I'm not going to talk about that because that research is still not quite settled as much, but this idea that bacteria can talk to other species is pretty well established. So I'll just highlight that really quickly. And they do this making this molecule called autoinducer two, which is super creative. but all bacteria make Most bacteria that we know of make this molecule across the spectrum, so my bacterium pseudomonas can make it, E. Coli can make it, and they'll put that out into the environment very similar to those other quorum sensing molecules. And this basically allows bacteria to say how many of you are there, how many of me are there with my specific molecule that I showed you earlier, and then how many other bacteria might be out there. And this is one way bacteria can kind of take count and make a decision about, should we behave as a group, should we launch an attack? Are these bacteria that we could get along with right now? So they're able to communicate in that way and send out signals to each other of, "I'm here, you should watch out, or, "Hey, let's be friends." And, again, this is still kind of not as well understood as some of those o- other quorum sensing, things, but it is pretty cool that bacteria can talk to other types of bacteria, which makes sense because there's so many different types just on our bodies alone. And just to make it a little bit more complicated so you can appreciate how complex bacteria are, this is an example of four different quorum sensing systems in one bacterium. So this is my bacterium pseudomonas, and it has these two here in the yellow and orange, the REL and the last, and these are very similar to what we see in the vibral fissure eye and how they function and how they work and the type of molecules they make. So that makes sense. That's pretty universal across all bacterium to have that type of system. But then it also has this other system, the PQS system, pseudomonas quorum sensing system, which is unique just to pseudomonas, because it's a diva. It has to have its own thing, and it has a completely different group of molecules you can see here in the grain called alkalquinolones. And this is just me nerding out a little bit about my own research project to show you this, um, because our lab specifically does study this, PQS system. So even within a single bacterium, there can be many different mechanisms of communication going on, um, using this quorum sensing system and they all are gonna accomplish a different task. So it's very complicated and you could spend your entire research career, which my advisor has, studying just one system in one bacterium. So if we think about communication and biofilms and kind of wrapping it up as far as what does this social behavior mean, what is it, how, how is it actually carried out in the wild? We can see here a biofilm actually forming on a liquid surface. So we're looking down at a beaker field with media and there's a biofilm forming right on the top of it. And again, you can see those wrinkles and those 3D structures forming. And if you're thinking about putting molecules out into the environment for other bacteria to sense that you're there, something as complex as a biofilm is going to change how that looks. And these are just some examples to think about. and a- another big question in our research group is how do we mimic the actual environment to actually understand how bacteria behave? Because we knew, you know, we've come a long way from just studying these bacteria swimming around by themselves and now we're like, oh, they do behave very differently. They behave in these biofilms, uh, very differently than they do in these liquid cultures. But then if we think about a biofilm, those can look very different as well. We might have very thick biofilms where only some of the bacteria are behaving in this quorum sensing way because they can't get those molecules to reach all the way to the top. So only some of them might be engaging in group behaviors. We might have flow, like I talked about with catheters in urine, where it's not always constant flow, but every once in a while there might be something coming in to wash away those signals and the bacteria have to start over. We can have very large biofilms where the concentration of those molecules can vary. And on this one, here we might have some ups and downs. It's pretty obvious and even in 2D how, how three-dimensional that those biofilms are, so we can have, again, pockets of bacteria behaving differently, communicating differently, even within a single species of biofilm. I don't know if this video will play, I don't think it will, but that's okay. basically this is go- would show you that, yes, in fact, if we have these big, deep wells where bacteria can fall into them and we're running fluid across the top of it, only the bacteria that are staying in these pockets are engaging in any type of communication related to that quorum sensing. So at the top, the molecules are being washed away and there's no communication really happening because the molecules aren't sticking around. So if we think about this is kind of designed to mimic some of the folds of the intestines where bacteria might be, you know, squeezed in, it can be really diverse even within a single biofilm.

Disarming Bacteria Not Killing

Speaker 2 41:15

And the last thing I'll kind of end on here is if, again, taking it into human health and, okay, this is really cool, bacteria can talk, they can make biofilms, but what does that mean if we're thinking about the antibiotic resistance crisis that we have right now, where bacteria have found ways to evade a lot of our treatments, and that's because when we d- have developed antibiotics over the past several decades, they've really been targeted to try to stop bacteria from being able to grow, to divide, essentially killing the bacteria altogether. But there's this new idea that's been, um, being explored in a lot of research right now of can we just cut off their communication entirely? So making them blind, deaf, and mute so that they can't hear or speak to each other. They can still survive, so they might not be motivated to figure out how to become resistant, but they're not gonna be able to launch those really vicious targeted group attacks in an infection. And it turns out we can do that. this video probably will not play, but yes, we can add a drug that makes bacteria deaf to each other, and they will not behave in a way that's pathogenic. They will survive, but they will not cause nearly as much damage as a bacteria that's able to hear each other and turn on those genes that make all the things that cause an infection. So this is a really cool, um, new urish field of study of approaching how we treat infections from disrupting the bacteria's ability to be social, and it's pretty promising right now. so the last thing I wanna show you guys, and maybe this one will play, I'm not sure, but if it doesn't, I'm gonna pull it up real quick if that's all right. so bacteria are incredibly social and complex, and I wanna show you this video from our lab website that was the first thing I saw when I walked into my advisor's office. This is for the first time, and he showed me this video, and I was like, "I think I wanna work with you. it's this video of pseudomonas originosa, and it's really fuzzy because this was a long time ago he took this, but what we have here is four bacterial cells chilling out. They're laying flat on a glass slide, just hanging out, and maybe a little bit of wiggle, a little bit of movement, and then all of a sudden pops up and walks off. It literally sits upright and walks off the screen, and this was the first time this was observed, and it was super cool, and I really fell in love with this idea, because you can kind of see it right then and there, looking like a little human, just kind of walking off, and I've bec- really started to intrigue me as far as, "Oh, these bacteria are not just these nasty things that give us a three week cold, or cause my kid to have an ear infection, and even cause really, devastating infections as well." And I wanna just bring us back to what Luv and Hawk said about these animal- antimolecules that were in such enormous numbers that seemed to be alive. And I really hope that showing you some of these super cool things bacteria can do and not just talking about the bad things they do, can help you appreciate all the bacteria that make up who you are and how important they are, and how d- sophisticated and dynamic they actually are, and maybe peak your curiosity about an i- this idea of intelligence. We think a lot about artificial intelligence these days, but what about microbial intelligence? What does it mean to be intelligent? And again, this idea of what actually is multicellular, what is single, single cell, and things are not always as cut and dry as they seem. Even in science where we do such rigorous research, there's still so many questions because biology is so dynamic and so complex. So I'm so grateful I was able to show you guys some of the research that we do and talk to you a little about my little nerd passion of bacteria. So thank you to, everybody who has helped me so far on my PhD journey and for Notre Dame and IUSB and the library here for letting me come talk to you guys and my lab, who's fantastic and awesome. and I would be happy to answer any questions that you guys have, especially, uh, if you have any comments about what was like to doodle and draw during the science talk, that would be cool as well. so thank you so g- guys so much for coming out tonight and hearing about bacteria. Yeah.

Audience Q&A

Speaker 3 46:09

In regards to behavior with the cut off since the majority of bacteria actually are nonformable, and so is, is there a way to control that so that non-confolding still do their thing while you're, you know, getting rid of the pathogenics?

Speaker 2 46:30

Sure, that's a really good point. there, I don't study the designing of the therapeutics myself, but what I have read is because they're, they're so species specific, those molecules, right? They're so, that was just a small handful of them. We can design ones that will be specific to only the pathogenic bacteria, which again, is really beneficial if we're thinking about, like, I'm on broad spectrum antibiotics right now, so it is killing a lot of good bacteria because it doesn't know how to discriminate against that, and that can be harmful, but the ability to really be species specific with some of these corum sensing, corum sensing inhibitors is what they're called, definitely could address some of those issues with messing with the good bacteria as well. Yeah.

Speaker 3 47:19

Biofilms. I'm wondering how specific they are to species or is that more of the is kind of.

Speaker 2 47:34

Yeah, the biofilms are, can vary widely. Even within a single species biofilm, we know that there's chemical changes. that's actually something our lab really focuses on is being able to take chemical signatures throughout one biofilm and they can be widely different, within a single biofilm and then even changing the type of nutrients that you give it can, can change the entire structure of the biofilm as well as the chemicals that we can detect. So, yeah, biofilms are incredibly diverse and one day they can look one way and then they might Uh, there's also a lot of mutations that can happen within a biofilm. So they start off genetically identical and then they lose genetic information or pick up some genetic information and the next day you could have a totally different looking biofilm. So they're very dynamic. You're not there, you know, we can get them as consistent as we can in the lab, but they're really, um, responsive to the environment and, and have really distinct, biochemical signatures as well.

Speaker 4 48:38

Yeah. The, this discussion about like how the, bacteria communicating with each other reminds me a lot of like ants and highs mentality of-

Speaker 2 48:47

mm-hmm.

Speaker 4 48:48

Things like that. Has there been any research like around like, you know, what, if this is a good metaphor or anything like that?

Speaker 2 48:57

Yeah, I've definitely seen some research that compares them specifically to hive mentality. there is a lot of correlation. So again, I think it raises an interesting question of are, you know, we kind of say, oh, it mimics us, but really this, this pattern seems to have worked through so long throughout evolutionary history that we can see some of these things in bacteria. so I have seen hive mentality and, and some of those patterns mentioned, and, and, specifically in like, some of these motile things I showed you that swarming where they're spreading out, they'll actually leave chemical signatures behind as well to tell bacteria don't go back there. We've already been there before. Um, so there is a lot more complex things than, than kind of the simplified version that we see in insects and some of these hive, organisms as well, yeah. Yes. Do the colony biofilms depend on what nutrients they have? Color. Oh, yes, yes, yes. so some of these biofilm images I showed you, they're, not true color. Some of them are, have been colorized by a computer, but some of them are colored. And yes, nutrients can change what color, these biofilms look like. Specifically, I'll kind of just go back real quick and show you, uh, one picture so I can use it as an illustration. these aren't biofilms here, but if I were to, to grow these in a biofilm, these, my specific bacterium will only make these when it's grown on an amino acid called glutamate. So that's the type of sh- of carbon it's using to eat, and when it has that, it will make this blue pigment all the time. My entire plate will turn blue. So yes, we can change some of these behaviors and when they turn on and how strong they are based on the food that we give the bacteria, for sure. That's a great question.

Speaker 3 51:03

Is the biofilm, um, actually waste from the bacteria or is it a secretion on purpose?

Speaker 2 51:09

It is a secretion on purpose. So there is waste present in there. They're able to get rid of it through some of those channels that we saw, but it is a purposeful secretion, that, again, can be very species specific, so not every biofilm is gonna have the same composition of sugars and proteins. Um, it's gonna depend on the bacteria, but it is intentional to kind of build up that protective environment for sure. But there is some waste in there, yeah.

Speaker 5 51:38

If there's quite a lot of other work going on in biofilms at Notre Dame, I know we have Watauga here at part of this series on urinary catheters- mm-hmm. in that film, and then also Notre Dame out of St. Patrick's Park has that facility, those artificial streams where they're studying the biofilms on the rocks and stuff, and there's a lot of other stuff.

Speaker 2 51:57

I think there's a few other research labs that are doing different types of biofilms. I believe that there is, um, a couple that look at biofilms looking at, like, tuberculosis models. I don't, they don't actually use, uh, the tuberculosis bacterium, but, an avian or a fish infection one. So there are some other labs at Notre Dame that do do biofilms, and a lot of them are a little bit more, infectious disease specific, like, I believe that would have been, uh, Ana Flores Morales, from Notre Dame who does those. But our lab is really the only one that's kind of studying it from a behavior perspective as opposed to an infection model perspective.

Speaker 3 52:43

Are you looking at me, sorry? so, uh, beautiful pictures tonight, a very nice talk. I really enjoyed it. It basically beautiful visuals. So I'm also, uh, very interested in the colony growth of a pseudomonas. Mm-hmm. So you are showing some analogy to treat, uh, ring, treat- Uh-huh. a ring or bone growth. Mm-hmm. So each bacterial cell in the colony would consider it as a pure culture, right? But the, there, there's a hesi genius, but yet they still grow into this, uh, same pattern. So it's, it's almost like the development, the developmental body, you know, so it's controlled by gradient of chemicals.

Speaker 5 53:28

Mm-hmm.

Speaker 3 53:28

So do you guys know anything about this kind of a chemical gradient in this, colony structure that would turn out to be this very beautiful, uh, structure? Like some of them serve as a framework, some of the, you know, uh, some of them, do other things, in the, this structure thing.

Speaker 2 53:52

Yeah, that's a very good question. And, like I mentioned with Dr. Marr's question, yes, there is definitely a gradient of s- we specifically look at the PQS corm sensing molecules, so those alque quinolones, and there's definitely a gradient of those throughout the biofilm, and also, there's different timing when we see them show up, that we can correlate to growth, or, you know, if we introduce a competitive species, that also is gonna change that gradient and when those are turned on. and we have a paper that should be coming out really soon that looks at some of these structures within the biofilm and what they're made of. we don't really know what the purpose of them is, but it does really correlate to where we find these pockets of molecules kind of ending up aggregating together. as far as kind of synchronizing the growth aspect of it, I'm not, I don't 100% know what that kind of gradient looks like, but we do know that as we kind of, take slices into the biofilm, we see, pretty consistent gradient changes within, within that, specifically looking at quorum sensing molecules. Other molecules that might be in play with some of these growth things, we haven't really looked at as much, but just from the communication perspective, yes, we do see quite a bit of gradients. So

Speaker 3 55:11

this literature I use for my microbiology and to get the candles course as through modus. Mm. So does the green color always show up before the blue hearts? Uh, because it should not in one spot, you never know whether, why this spot, it shows the pseudo- Yeah.

Speaker 2 55:31

Yeah. My, the, the strain of pseudomonas that I use does not typically show up as green or blue, like consistently. It, it does not make that piocyanin molecule. It doesn't, it doesn't turn blue or green, unless I give it specific nutrients. Now, if we look at some of the other strains that are more associated with infection, then the, the changes in those blue green colors are gonna be a lot more consistent and, um, the, the regulation of when it's blue and when it's green is also gonna be a little bit more nutrient dependent as well, but I don't really s- look at those more infectious strains. Ours is pretty domesticated and tame and doesn't really have a lot of those things on a daily basis, so I can't really answer for sure.

Speaker 6 56:27

So the, um, biofilms that would work in the body are, what would we cause the infection or data for bad bacteria or would it take if that sugar itself or a little message or something today or a little molecule?

Speaker 2 56:43

So even good bacteria in our bodies are gonna be able to form some biofilms. Now, inside of us is not really super solid. There's a lot of liquid moving around in our bodies. So, it's kind of a hybrid, of a biofilm in some ways and a lot of motility like this thing here where they're, spreading out. So, the really thick, dense, surface attached biofilms that we see on surfaces aren't necessarily happening, happening quite like that inside of us. Now on our teeth, definitely those are biofilms. And if we don't brush them, then yeah, that's gonna start to cause some problems because those bacteria will be able to start to rot away at our teeth. but having a biofilm does not automatically mean that you're going to have an infection, but they are if a bacteria does start to form a biofilm on maybe an open wound or a catheter or some type of implant, those are just really difficult to treat with antibiotics. They're gonna be protected by antibiotics and they're gonna be physically hard to remove as well. But biofilm and infection are not necessarily the same, thing, and good and bad bacteria can form them.

Speaker 6 57:49

So the current phages.

Speaker 5 57:56

Phages? Yeah,

Speaker 6 57:58

but I understand that phages was something they use higher antibiotics to try to use the covids, I guess.

Speaker 2 58:06

So, yes. Phages are, viruses that kill bacteria. Yeah, yeah. No, that's okay. So bacteria phages, we call them phages for short usually. Yes, those can be used as antibiotic treatments as well, because they will kill typically only bacteria, and they can also be pretty species specific. They might not kill every bacteria, they'll only target maybe a couple different types of bacteria. So phage treatment is still pretty popular and it's growing because it doesn't have as many of the bad side effects as antibiotics have, and you can be a little bit more targeted But yeah, phages are viruses that will kill bacteria and hopefully, if you're using the mistreatment, only kill the bad bacteria.

Speaker 6 58:51

How do you bad bacteria bacteria in the young levels?.

Speaker 2 58:59

They do. They have a lot of different mechanisms. That's an entire other field of study of, how they can fight off these vir- these phages. And one of the cooler mechanisms is basically they have like a needle they can shoot out of their bodies and, and, puncture viruses that way. And, and a lot of the same ways that they might kind of cause an infection. In humans, they're also able to fight off, viruses and, and other bad bacteria. But the, the world of viruses and phages is, is very complex and we're still discovering new phages every day that infect bacteria. So it's a whole world that we are still exploring, but yeah.

1 59:38

Do we have one more question?

Speaker 5 59:42

I used to use a grid of water filter and I was not very consistent in cleaning it and I would pull the thing out and it would be slippery on the surface and the bottom of these slipperiness like I should stop you. But was that a dangerous biofilm that would form on tap water?

Speaker 2 59:57

I'm gonna guess that if it's probably not dangerous per se, because even though, you know, we live in a place where most of our water's pretty safe to drink anyway, so I'm not a doctor. I probably wouldn't drink it myself just because I'd be a little grossed out, but, yeah. Yeah, it's, it's, you know, I think, I think more often than not, bacteria are not going to do a ton of damage to you. We, uh, we're encountering them. You know, you, you cook your food, you're still gonna be ingesting bacteria, throwing your fruits and vegetables. So most of the time, I think it's safe to assume that you should just live your life as is. And, if you see something slimy, I, you know, say better safe than sorry, I suppose. But yeah.

Closing Thanks

1 1:00:43

Let's thank, uh, Maggie for a great time. And I, I wanna thank you for coming out tonight. we have coming up Uh, so February 6th will actually be just down the hall in the ballroom, and we're gonna be folding. so there will be paper, we'll be making orgami. So Kyle Schweiderman is a teaching professor in mathematics at IOSB, and he's gonna be leading us in the mathematics as well as the art of orgami, so that's coming up. and the other thing that I wanted to mention is that, all of these talks, are available at universerevealednD.edu, and Steve Tope, uh, has been filming these, and this talk, he'll add in the video links. So if you wanna check the website and see the video links so that you can see that, it'll be up in, in two to three weeks or so. So, I wanna thank you for coming out tonight, and I hope to see you February 6th.

1:01:47

Thank you.