Subtitles section Play video Print subtitles Bacteria are the oldest living organisms on the earth. They've been here for billions of years, and what they are are single-celled microscopic organisms. So they are one cell and they have this special property that they only have one piece of DNA. They have very few genes, and genetic information to encode all of the traits that they carry out. And the way bacteria make a living is that they consume nutrients from the environment, they grow to twice their size, they cut themselves down in the middle, and one cell becomes two, and so on and so on. They just grow and divide, and grow and divide -- so a kind of boring life, except that what I would argue is that you have an amazing interaction with these critters. I know you guys think of yourself as humans, and this is sort of how I think of you. This man is supposed to represent a generic human being, and all of the circles in that man are all of the cells that make up your body. There is about a trillion human cells that make each one of us who we are and able to do all the things that we do, but you have 10 trillion bacterial cells in you or on you at any moment in your life. So, 10 times more bacterial cells than human cells on a human being. And of course it's the DNA that counts, so here's all the A, T, Gs and Cs that make up your genetic code, and give you all your charming characteristics. You have about 30,000 genes. Well it turns out you have 100 times more bacterial genes playing a role in you or on you all of your life. At the best, you're 10 percent human, but more likely about one percent human, depending on which of these metrics you like. I know you think of yourself as human beings, but I think of you as 90 or 99 percent bacterial. (Laughter) These bacteria are not passive riders, these are incredibly important, they keep us alive. They cover us in an invisible body armor that keeps environmental insults out so that we stay healthy. They digest our food, they make our vitamins, they actually educate your immune system to keep bad microbes out. So they do all these amazing things that help us and are vital for keeping us alive, and they never get any press for that. But they get a lot of press because they do a lot of terrible things as well. So, there's all kinds of bacteria on the Earth that have no business being in you or on you at any time, and if they are, they make you incredibly sick. And so, the question for my lab is whether you want to think about all the good things that bacteria do, or all the bad things that bacteria do. The question we had is how could they do anything at all? I mean they're incredibly small, you have to have a microscope to see one. They live this sort of boring life where they grow and divide, and they've always been considered to be these asocial reclusive organisms. And so it seemed to us that they are just too small to have an impact on the environment if they simply act as individuals. And so we wanted to think if there couldn't be a different way that bacteria live. The clue to this came from another marine bacterium, and it's a bacterium called Vibrio fischeri. What you're looking at on this slide is just a person from my lab holding a flask of a liquid culture of a bacterium, a harmless beautiful bacterium that comes from the ocean, named Vibrio fischeri. This bacterium has the special property that it makes light, so it makes bioluminescence, like fireflies make light. We're not doing anything to the cells here. We just took the picture by turning the lights off in the room, and this is what we see. What was actually interesting to us was not that the bacteria made light, but when the bacteria made light. What we noticed is when the bacteria were alone, so when they were in dilute suspension, they made no light. But when they grew to a certain cell number all the bacteria turned on light simultaneously. The question that we had is how can bacteria, these primitive organisms, tell the difference from times when they're alone, and times when they're in a community, and then all do something together. What we've figured out is that the way that they do that is that they talk to each other, and they talk with a chemical language. This is now supposed to be my bacterial cell. When it's alone it doesn't make any light. But what it does do is to make and secrete small molecules that you can think of like hormones, and these are the red triangles, and when the bacteria is alone the molecules just float away and so no light. But when the bacteria grow and double and they're all participating in making these molecules, the molecule -- the extracellular amount of that molecule increases in proportion to cell number. And when the molecule hits a certain amount that tells the bacteria how many neighbors there are, they recognize that molecule and all of the bacteria turn on light in synchrony. That's how bioluminescence works -- they're talking with these chemical words. The reason that Vibrio fischeri is doing that comes from the biology. Again, another plug for the animals in the ocean, Vibrio fischeri lives in this squid. What you are looking at is the Hawaiian Bobtail Squid, and it's been turned on its back, and what I hope you can see are these two glowing lobes and these house the Vibrio fischeri cells, they live in there, at high cell number that molecule is there, and they're making light. The reason the squid is willing to put up with these shenanigans is because it wants that light. The way that this symbiosis works is that this little squid lives just off the coast of Hawaii, just in sort of shallow knee-deep water. The squid is nocturnal, so during the day it buries itself in the sand and sleeps, but then at night it has to come out to hunt. On bright nights when there is lots of starlight or moonlight that light can penetrate the depth of the water the squid lives in, since it's just in those couple feet of water. What the squid has developed is a shutter that can open and close over this specialized light organ housing the bacteria. Then it has detectors on its back so it can sense how much starlight or moonlight is hitting its back. And it opens and closes the shutter so the amount of light coming out of the bottom -- which is made by the bacterium -- exactly matches how much light hits the squid's back, so the squid doesn't make a shadow. It actually uses the light from the bacteria to counter-illuminate itself in an anti-predation device so predators can't see its shadow, calculate its trajectory, and eat it. This is like the stealth bomber of the ocean. (Laughter) But then if you think about it, the squid has this terrible problem because it's got this dying, thick culture of bacteria and it can't sustain that. And so what happens is every morning when the sun comes up the squid goes back to sleep, it buries itself in the sand, and it's got a pump that's attached to its circadian rhythm, and when the sun comes up it pumps out like 95 percent of the bacteria. Now the bacteria are dilute, that little hormone molecule is gone, so they're not making light -- but of course the squid doesn't care. It's asleep in the sand. And as the day goes by the bacteria double, they release the molecule, and then light comes on at night, exactly when the squid wants it. First we figured out how this bacterium does this, but then we brought the tools of molecular biology to this to figure out really what's the mechanism. And what we found -- so this is now supposed to be, again, my bacterial cell -- is that Vibrio fischeri has a protein -- that's the red box -- it's an enzyme that makes that little hormone molecule, the red triangle. And then as the cells grow, they're all releasing that molecule into the environment, so there's lots of molecule there. And the bacteria also have a receptor on their cell surface that fits like a lock and key with that molecule. These are just like the receptors on the surfaces of your cells. When the molecule increases to a certain amount -- which says something about the number of cells -- it locks down into that receptor and information comes into the cells that tells the cells to turn on this collective behavior of making light. Why this is interesting is because in the past decade we have found that this is not just some anomaly of this ridiculous, glow-in-the-dark bacterium that lives in the ocean -- all bacteria have systems like this. So now what we understand is that all bacteria can talk to each other. They make chemical words, they recognize those words, and they turn on group behaviors that are only successful when all of the cells participate in unison. We have a fancy name for this: we call it quorum sensing. They vote with these chemical votes, the vote gets counted, and then everybody responds to the vote. What's important for today's talk is that we know that there are hundreds of behaviors that bacteria carry out in these collective fashions. But the one that's probably the most important to you is virulence. It's not like a couple bacteria get in you and they start secreting some toxins -- you're enormous, that would have no effect on you. You're huge. What they do, we now understand, is they get in you, they wait, they start growing, they count themselves with these little molecules, and they recognize when they have the right cell number that if all of the bacteria launch their virulence attack together, they are going to be successful at overcoming an enormous host. Bacteria always control pathogenicity with quorum sensing. That's how it works. We also then went to look at what are these molecules -- these were the red triangles on my slides before. This is the Vibrio fischeri molecule. This is the word that it talks with. So then we started to look at other bacteria, and these are just a smattering of the molecules that we've discovered. What I hope you can see is that the molecules are related. The left-hand part of the molecule is identical in every single species of bacteria. But the right-hand part of the molecule is a little bit different in every single species. What that does is to confer exquisite species specificities to these languages. Each molecule fits into its partner receptor and no other. So these are private, secret conversations. These conversations are for intraspecies communication. Each bacteria uses a particular molecule that's its language that allows it to count its own siblings. Once we got that far we thought we were starting to understand that bacteria have these social behaviors. But what we were really thinking about is that most of the time bacteria don't live by themselves, they live in incredible mixtures, with hundreds or thousands of other species of bacteria. And that's depicted on this slide. This is your skin. So this is just a picture -- a micrograph of your skin. Anywhere on your body, it looks pretty much like this, and what I hope you can see is that there's all kinds of bacteria there. And so we started to think if this really is about communication in bacteria, and it's about counting your neighbors, it's not enough to be able to only talk within your species. There has to be a way to take a census of the rest of the bacteria in the population. So we went back to molecular biology and started studying different bacteria, and what we've found now is that in fact, bacteria are multilingual. They all have a species-specific system -- they have a molecule that says "me." But then, running in parallel to that is a second system that we've discovered, that's generic. So, they have a second enzyme that makes a second signal and it has its own receptor, and this molecule is the trade language of bacteria. It's used by all different bacteria and it's the language of interspecies communication. What happens is that bacteria are able to count how many of me and how many of you. They take that information inside, and they decide what tasks to carry out depending on who's in the minority and who's in the majority of any given population.