How Do Bacteria Talk To Each Other?

FLORA LICHTMAN: Hey, it’s Flora Lichtman. You’re listening to Science Friday.

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On today’s show, zooming in on the sophisticated secret societies living around and within us.

BONNIE BASSLER: They’ve been here for billions of years. They do evolution on a much faster scale. So they’ve had time to occupy every niche on the planet and to optimize.

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FLORA LICHTMAN: As humans, I think it’s tempting to imagine ourselves as the pinnacle of evolution. I mean, we talk, we make art, we build cool and transformative things, and we’ve changed the planet in profound ways. But there are life forms that have been on this planet evolving a lot longer than us, like, way longer.

Bacteria go back billions of years. What if they have come up with sophisticated playbooks that we just don’t yet understand? Could they have their own culture, their own language, their own complex societies that were ignorant of, even though they’re playing out right under, and perhaps even in, our noses?

Those are some of the questions that might next guest has been looking into for more than 30 years. Dr. Bonnie Bassler is a Microbiologist and runs a lab at Princeton University. She was awarded the National Medal of Science this year. Bonnie, welcome to Science Friday.

BONNIE BASSLER: Thanks, Flora. I’m delighted to be here.

FLORA LICHTMAN: What did you think of that intro, Bonnie, about how much of what bacteria are doing do you think we’re unaware of?

BONNIE BASSLER: I think a lot of what bacteria are doing, we’re unaware of. We know a lot about the parts, the parts list that make bacteria and other organisms. But the behaviors, the sophisticated, magical, astounding things bacteria can do, that’s been the focus of a lot of work for the past few decades. And in that realm, I think we’re only beginning to understand the complexity.

FLORA LICHTMAN: What about language? Is there an argument that bacteria have language?

BONNIE BASSLER: Well, since that’s my life’s work, I would say, yes. And so of course, bacteria– so just to set the tone a little bit, or set the stage a little bit, of course bacteria are microscopic. They’re single cells.

You can’t see them with your eyes. To see them, you need to look under a microscope. So they don’t have language the way you and I do. They don’t talk with words.

But what the field has shown is that they actually communicate with chemicals. So they use chemicals as their words and they use those chemicals to count how many neighbors are around, to take a census of who those neighbors are. Are they friend? Are they foe? Are they relatives?

Are they not relatives? And then they use the information, all of which is embedded in these molecules, to help them make decisions based on whether they’re alone or in groups, and who’s in the neighborhood.

FLORA LICHTMAN: How well do we understand how that chemical sensing works?

BONNIE BASSLER: So we actually do understand a lot about that. So this field is a very vibrant field. The field is called quorum sensing, that the bacteria sense when they’re in a quorum, and then they do things as groups. And we understand some about what the molecules are. We know some of the molecules.

We understand something about how they’re detected. We understand something about how the bacteria integrate the information and how they decode the information that’s embedded in these molecules. And we know a lot about what they do when they’re alone and when they’re in groups.

FLORA LICHTMAN: I mean, that sounds like they’re sending messages. But are they also conversing back and forth? Does the relay go more than just one stop or two stops?

BONNIE BASSLER: So it’s not exactly a conversation, like you asked me a question and I give you a different answer, and then you interpret what I say and ask me the next question. So far, as we understand now, and of course, for sure, there’s more to find out, what we think that they’re doing, the simple things they’re doing is they’re using molecules that build up outside of the cells as the cells grow.

And so the molecules– the amount of molecules around the bacteria track with how many bacteria are there. So first, they use it to count. They say, am I alone or am I in a group, because they want to behave differently when they’re alone and when they’re in groups.

When they’re alone, they carry out tasks that a single bacterium can accomplish. But they don’t bother to do tasks that it takes lots of bacteria acting together to make the task successful unless they’re in a group. So the first thing they do is they say, am I alone or am I in a group?

And then they do tasks A, B, or C, or D, E, or F, and those tasks become successful depending on how they get carried out. And then the second more sophisticated thing they do with those molecules, because there’s a blend of these molecular words, they ask, who is around me? Is it my twin, is it my cousin, or is it the enemy?

And then they changed the tasks that they carry out based on whether they’re surrounded by family and friends or the enemy. So they share and they do nice group behaviors when they’re surrounded by their siblings. And then when they’re in competitive environments, they try to kill the other guy, or they try to keep their goodies to themselves, and they’re not as available for sharing.

FLORA LICHTMAN: Give me an example of a behavior that they would do just with friends and family, and then a behavior they would do amongst foes?

BONNIE BASSLER: So bacteria often consume solid food. So they need to take little bites out of it. And so what they’ll do is they will secrete enzymes outside of themselves that chew up solids into small enough bits that a single bacteria can take those bits up.

But of course, if you put your enzyme out, it chews those bits up. The bits are floating around, and your neighbors can get them. So those are called public goods. Some solid substrate gets chewed up into all these bits and then everybody gets some of the pie.

So that, they will do with their friends and family, because they’re going to make an expensive enzyme that they have to put out of themselves to chew up the solid food. And then anybody can get the products. So you want to do that if you’re surrounded by your friends. It’s like you’re feeding your family. It’s a group dinner, family-style dinner.

FLORA LICHTMAN: Sunday dinner. Yes, we’ve all been there.

BONNIE BASSLER: Yes. Exactly Right. Dig in. OK, so that’s something– for example, public goods and sharing the effort of your work, bacteria will do when they’re around their families. But you don’t want to share if it’s your competitor that’s eating up all the food.

So they typically won’t do those kinds of behaviors, like public good behaviors, when they’re surrounded by foe. And so in that case, they’ll do other things, like make poisons that they are immune to and that kill off their competitors. They put them out and then they try to outwit or get rid of their competitors. And so those are all group behaviors. But it matters who’s in the neighborhood, which set of group behaviors get taken.

FLORA LICHTMAN: And are they sensing other bacteria? Do they recognize viruses?

BONNIE BASSLER: Yeah.

FLORA LICHTMAN: What do they know about who’s around them?

BONNIE BASSLER: And so that’s actually the forefront of this field. And so if I go back a little bit, we used to– in the beginning of this field, I should just say it was astonishing 30-some years ago, or even more than that now, when it was discovered that bacteria had the capacity for group behaviors.

It was always thought that bacteria were sort of asocial and dumb. They divided in half and each bacterium did its own thing. They didn’t have the sort of genetic capacity to there were others around.

And so in the beginning of this field, the first thing scientists thought was when they realized there were molecules that these bacteria were releasing, the molecules were increasing in proportion to cell number, and then the bacteria would do behaviors as a group. The first thing we thought is that they know that they’re around their siblings.

Then after that, we realized there’s more than one molecule in this language. Then there was a molecule that was for the cousins. So first, there was the species, then there was the genera, the family, and then there was an Interspecies molecule so they could talk across species boundaries.

And now what we’ve learned, and this is only in the last few years, is that they can actually detect if they’re in a host. So they can detect molecules made by human gut cells. They can detect, for example, if they’re in your digestive system.

And then also, bacteria– just like we are bombarded by viruses, bacteria are also attacked by viruses all the time. And so, in fact, these viruses have evolved the capacity to listen in to these bacterial conversations. They’re eavesdroppers and they can recognize when there’s lots of bacteria around.

And that’s a good time for the virus, the predator, to attack the bacteria. So now we’re thinking that these quorum-sensing conversations span all domains, from viruses, to bacteria, to eukaryotes, to mammalian cells. And so the field is still in its infancy, in a way, even though we do know a lot about the molecules, and how they detect them, and how they decode information. I still think– well, I need a job. And so I still think that these bacteria– that were only at the beginning of understanding the complexity and the capacity of these chemical conversations.

FLORA LICHTMAN: Well, what I’m thinking is, these bacteria inside me know more about me than I know about them.

BONNIE BASSLER: No question. But they’ve had a longer time. So they’ve had billions of years to evolve in the recent history. And they have been evolving in collaboration, or in competition with, higher organisms.

But yeah. So they’re tuned in to all of this information. They’re sort of like little computer chips, that they’re taking in all kinds of information. And then moment to moment to moment, they turn on and off genes, which lets them turn on and off behaviors. And that’s how they succeed.

And it’s very similar to what we do. It’s sort of a stripped down version of us.

FLORA LICHTMAN: Well, yeah. That’s the thing. I mean, not to be all big thinky here, but I think we feel like we have a monopoly on decision making.

BONNIE BASSLER: Yeah. We think we’re these rarefied, special organisms on Earth. And I do think I’m charming.

FLORA LICHTMAN: You are special, Bonnie.

BONNIE BASSLER: Yes. Thank you very much. But anyway– but yeah. So the truth is that we evolved from bacteria. Every organism evolved from bacteria.

They’ve been here for billions of years. They do evolution on a much faster scale because they divide every 20 or 30 minutes than human beings or higher organisms do. So they’ve had time to occupy every niche on the planet and to optimize.

And this sort of logical decision making that you’re talking about, Flora, in a bacterium, they don’t have brains. They don’t have consciousness. They don’t have feelings like we do. We are special, in some way.

But in the simplest sense of the biochemistry and the genetics that goes on in any living organism, these decisions are very analogous to one another. Information comes in and then bacteria, and we, behave in a way, in the case of the bacteria, that allows them to succeed.

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FLORA LICHTMAN: We’re going to take a quick break, but don’t go away. When we come back, how Bonnie got into this field.

BONNIE BASSLER: It started as simply a question about how can a bacterium be part of a group? They seem to be too primitive and too stupid to be able to do that.

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FLORA LICHTMAN: I mean, do you think that my anthropomorphizing questions are problematic? Where do you fall on that idea?

BONNIE BASSLER: No, I anthropomorphize everything because I think it’s an easy way to understand it. They are communicating. They are knowing friend from foe, family. They’re making decisions.

I think thinking about bacteria and their language, which we’ve talked about, is chemical. It’s not words, it’s chemical. But the chemicals are the words. And being able to extract from those chemicals not only how many neighbors are around me, but who the neighbors are, I think anthropomorphizing that is a good idea, because it is the progenitor of our language and our ability to self from other friend, from foe, and to make individual decisions and group decisions. And so I don’t think that’s a wrong way to think about it.

FLORA LICHTMAN: It’s the foundation for our own behaviors.

BONNIE BASSLER: They are the foundation for us, so yes. I think– OK, I’m brainwashed. I do think it is the foundation for our own behaviors.

And then when we really think about what these bacteria are trying to accomplish by deciding, can they do something alone? Can they do something in a group? We make those kinds of decisions all the time.

The behaviors did build on one another through evolution. So why not think about them– use similar words to describe them as we do for, say, humans?

FLORA LICHTMAN: Yeah. We need to bacterium-morphize ourselves or something. Personally, how much are you driven by practical applications, like that cracking bacterial communication could help fight diseases?

BONNIE BASSLER: Well, so that is a big theme of my team’s work. I am a do-gooder at heart. And if I really confess to you, when I started this, that’s not what I thought. This whole field started in an obscure but beautiful bioluminescent bacterium that what it did as a group was turn on light.

And that made the invisible world of the bacteria visible to the scientists. And it gave us something to track. We could see that they only made light as a group. And so my question back then was, how do they know to do that?

How can they do that? This is how bacteria get any bang for their buck. They know when they’re alone. They know when they’re in groups. And they act accordingly.

But back then, there was no biomedical, or industrial, or ecological significance to the work. It was just the example that we had. And what we thought back then was we wanted to understand how does any collective behavior work on Earth.

How can organisms carry out tasks in groups and accomplish things that they couldn’t accomplish as individuals? And of course, for me, working on bacteria, they’re very– not that anybody believes this after this conversation, they are much simpler organisms.

They’re fast growing. They’re clones of each other. You can have a surprise in the incubator every eight hours to do your studies.

And so that was super attractive to ask questions about collective behaviors, just as what we would call a model system for group behaviors. But then, lo and behold, what was discovered in these bioluminescent bacteria ended up being discovered in tens of thousands of kinds of bacteria, including pathogens, including industrially-relevant bacteria.

And we now know that being able to act in groups is critical for bacteria to be pathogens. It’s critical for them to do what they do in the environment. It’s critical for them when they clean up oil spills and pollution.

And so we kind of pat ourselves on the shoulder for oh, weren’t we smart to be working on this glow in the dark bacteria? Because it led the way to all these fantastic, fantastic biomedical and industrial applications. And so now I’m very into that. Very, because I do want this all to matter more than just in an academic sense.

Now I realize, it started as simply a question about how can a bacterium be part of a group? They seem to be too primitive and too stupid to be able to do that. And it did, over many decades, and many labs, change to this very, I hope, important biomedical industrial question. But I didn’t know that at the beginning.

But of course, again, that’s what a scientist does. The science takes us on this adventure. We started on this adventure. And then we’re like, hey, these pathogens need this to be pathogens.

Could we make bacteria that can’t talk or can’t hear and those could be new medicines? Could we beef up the chit-chat in bacteria that are beneficial and help make the world or make us healthier? That is what scientists do.

Even if that wasn’t the original theme that started it all, we’re always looking for applications for humanity or for the Earth. And so I think we did always dream it would be bigger than that one bioluminescent bacterium. But it took a while to get there.

FLORA LICHTMAN: Well, how did you get into this field? I mean, did you set out to study bacteria.

BONNIE BASSLER: No, that was by accident. So my shaggy dog checkered past. I went to college to be a vet. So I always loved nature. I loved animals.

You have to remember, I’m old. And so when I was young, I’d never met a scientist and girls didn’t really become doctors and I loved these animals. So my parents were always like, do you want to be a vet?

You want to be a vet. You want to be a vet. So I thought, oh, I want to be a vet. Oh, I want to be a vet. And so I went to college to be a veterinarian, and I only lasted a couple of weeks because there was a lot of blood and gore involved.

And I was like, oh, shoot. I like live animals. I don’t want to cut them open. I don’t want to see their insides.

And so anyway, the real truth is I was completely lost right after I got to college. But there was a bulletin board that I didn’t– I liked biology classes. I liked chemistry classes. And there was a bulletin board that had professors that would let you work in a lab.

And so I thought, I wonder what that’s like? And so I literally went to this lab and the professor had a bacteria project and a cancer project. And so I thought oh– I was 19 years old. I’ll cure cancer. Right?

FLORA LICHTMAN: Sure. Yeah.

BONNIE BASSLER: Do something important, as you’ve sort of been discussing with me. And so I went to the lab and he put me on the bacteria project. And I’m like, oh, no. This is the stupid project.

He’s putting me on this. This is a test. And if I try hard and I’m earnest, maybe then he’ll move me to the important project.

Well, Flora, it’s a few years later, and here I am, because I just fell in love with bacteria as model systems to study things that are about human biology and about biology in general. I really liked, in some way, this simplicity and the complexity.

I don’t know if that makes– I hope that makes sense in the context of what we’re talking about. I mean, they are simple organisms. They’re single cells. They don’t have brains. They don’t have all these complex behaviors. But they have behaviors that are complex enough to have captured my attention.

FLORA LICHTMAN: They do a lot with a little.

BONNIE BASSLER: Yeah, exactly. They have no fluff. In some way, they’re kind of perfect, each of them for their own niche. And bacteria have been model systems.

I mean, that’s how we know about DNA, RNA, and proteins. And the molecular biology revolution, it all came from bacteria and viruses. And so the truth is they’re not solved yet.

And so it was thought of that bacteria gave us the parts list, like I just said, DNA, RNA, and proteins, and that higher organisms were going to give us all the cool stuff. Behaviors, appendages, body parts, development.

So there was a point when bacteria were a little bit out of vogue, that turned out to be right when I was starting my career, because it was thought that the good secrets had already– that bacteria possessed had already been found. But lo and behold, scientists kept at it, those of us who loved bacteria.

And then we found out that beyond giving us the amazing parts list of the parts that make a living organism, they do have all these behaviors. The one we’re talking about, communication, collective behaviors. They have body plans.

They put the right things in the right places, just like you have arms, legs, head in the right place at the right time. Bacteria, it turns out, they were just so small you couldn’t see that back then.

And they do all of these terrible and magical things. So I think, for me, they’ve given me, a way to study those kinds of biological questions, but in this simple system. That’s a long answer for me wanting to be a vet. Yeah.

FLORA LICHTMAN: Before we let you go, what is your top burning bacterial question? What is the thing that you want to, above all else, before you leave this mortal coil?

BONNIE BASSLER: Yeah. So my gang discovered that bacteria talk. They showed that they’re multilingual. They’ve showed that viruses eavesdrop.

They’ve showed that they can– that eukaryotic cells, higher organisms, are part of this conversation. What we’d love to do, like the horizon for us now, is to actually come out of the test tube with the single species of bacteria or a single virus and really gin up, somehow, scenarios that are more authentic, like many species of bacteria, together with viruses, with higher organisms in space and time, not all shaken around in a perfect environment.

Because if we’re really going to make applications either turn on, chit-chat when we want, or stop harmful bacteria from talking, it’s not going to get done in a test tube, shaking around in a perfect environment in Princeton, New Jersey. We have to be able to learn enough about how this works in the real world that we could safely, and reliably, and successfully manipulate it if we want to make applications.

And so going back to the first thing you said, for us, it’s all about complexity and trying to think up ever-more complex environments or scenarios to see how could this quorum-sensing, and bacterial communication, and group behaviors ever work outside of a test tube in a lab? It does. We know it does. But yeah, I think that’s our next 10 years.

FLORA LICHTMAN: I can’t wait to have you back to talk about it.

BONNIE BASSLER: Well, that would be a delight. And I can’t wait for that. I hope it’s not 10 years.

FLORA LICHTMAN: Thanks, Bonnie.

BONNIE BASSLER: Thank you.

FLORA LICHTMAN: Dr. Bonnie Bassler is a Professor of Molecular Microbiology at Princeton University in New Jersey.

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And that is about all we have time for. Lots of folks helped make this show happen, including–

JOHN DANKOSKY: John Dankosky.

ANNIE NERO: Annie Nero.

JASON ROSENBERG: Jason Rosenberg.

RASHA ARIDI: Rasha Aridi.

FLORA LICHTMAN: I’m Flora Lichtman. Thanks for listening.

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