And so 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. And what the squid has developed is a shutter that can open and close over this specialized light organ housing the bacteria.
And 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. So 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. And so this is like the stealth bomber of the ocean.
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% of the bacteria.
And so 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.
And so 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.
And so 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.
And 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. And so now 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.
And 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. So 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.
But 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.
So bacteria always control pathogenicity with quorum sensing. And so that’s how it works.
We also then went to look at what are these molecules – so these were the red triangles on my slides before. And so this is the Vibrio fischeri molecule. This is the word that it talks with.
And 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. So 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.
And what that does is to confer exquisite species specificities to these languages. So 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.
And so 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. So 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.
And so what happens is that bacteria are able to count how many of me and how many of you. And 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.