Princeton professor Bonnie L. Bassler has often been called the Bacteria Whisperer, and for a microbial biology researcher, that’s a high compliment. Bassler has made important contributions to her field of research, including discovering how bacteria communicate with one another. Her research has spurred development of an entire class of antimicrobial drugs that could potentially work by interfering with bacterial “quorum sensing.”
Bassler was born in Chicago and grew up in Danville, California, where she learned to love logic and problem solving from a young age. She went to UC Davis intending to be a veterinarian, but switched to biochemistry and genetics because she couldn’t dissect animals without passing out, she told the Proceedings of the National Academy of Sciences.
Her new line of study proved extremely fruitful. A Princeton professor since 1994, she was awarded a MacArthur Fellowship in 2002, and given numerous other awards for her research, including election into the National Academy of Sciences in 2006 and a fellowship at the American Academy of Arts and Sciences in 2007. Later this month she will collect another honor when the New Jersey Chamber of Commerce presents her with the Alice H. Parker Women Leaders in Innovation Award.
Bassler will speak at the reception and awards celebration on Thursday, September 22, from 5 to 8 p.m. at the National Conference Center in East Windsor. Tickets are $100 for chamber members, $125 for nonmembers. For more information, visit www.njchamber.com.
In addition to her involvement in groundbreaking research, Bassler has spent a lot of time communicating to the public. She recently gave a TED talk explaining how her research revealed the mechanisms of bacterial communication. Below is a transcript of her talk, edited for print:
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.
There are 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 the A, T, Gs and Cs 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.
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.
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. This bacterium has the special property that it makes light, so it makes bioluminescence, like fireflies make light.
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.
When a bacterial cell is 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 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. 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.
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 is that Vibrio fischeri has a protein. It’s an enzyme that makes that little hormone molecule. 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.
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 and we started to look at other bacteria, and these are just a smattering of the molecules that we’ve discovered. 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. 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.
Again we turn to chemistry, and we figured out what this generic molecule is. It’s a very small, five-carbon molecule. The important thing is that every bacterium has exactly the same enzyme and makes exactly the same molecule. So they’re all using this molecule for interspecies communication. This is the bacterial Esperanto.
Once we got that far, we started to learn that bacteria can talk to each other with this chemical language. But what we started to think is that maybe there is something practical that we can do here as well. I’ve told you that bacteria do have all these social behaviors, they communicate with these molecules. Of course, I’ve also told you that one of the important things they do is to initiate pathogenicity using quorum sensing. We thought, what if we made these bacteria so they can’t talk or they can’t hear? Couldn’t these be new kinds of antibiotics?
Of course, you’ve just heard and you already know that we’re running out of antibiotics. Bacteria are incredibly multi-drug-resistant right now, and that’s because all of the antibiotics that we use kill bacteria. They either pop the bacterial membrane, they make the bacterium so it can’t replicate its DNA. We kill bacteria with traditional antibiotics and that selects for resistant mutants. And so now of course we have this global problem in infectious diseases. We thought, well what if we could sort of do behavior modifications, just make these bacteria so they can’t talk, they can’t count, and they don’t know to launch virulence.
And so that’s exactly what we’ve done, and we’ve sort of taken two strategies. The first one is we’ve targeted the intraspecies communication system. So we made molecules that look kind of like the real molecules, but they’re a little bit different. And so they lock into those receptors, and they jam recognition of the real thing. By targeting this system, what we are able to do is to make species-specific, or disease-specific, anti-quorum sensing molecules. We’ve also done the same thing with the other system. We’ve taken that universal molecule and turned it around a little bit so that we’ve made antagonists of the interspecies communication system. The hope is that these will be used as broad-spectrum antibiotics that work against all bacteria.
We think that this is the next generation of antibiotics and it’s going to get us around, at least initially, this big problem of resistance.
We know that the principles and the rules, if we can figure them out in these primitive organisms, the hope is that they will be applied to other human diseases and human behaviors as well. I hope that what you’ve learned is that bacteria can distinguish self from other. By using these two molecules they can say “me” and they can say “you.” Again of course that’s what we do, both in a molecular way, and also in an outward way, but I think about the molecular stuff.
This is exactly what happens in your body. It’s not like your heart cells and your kidney cells get all mixed up every day, and that’s because there’s all of this chemistry going on, these molecules that say who each of these groups of cells is, and what their tasks should be. Again, we think that bacteria invented that, and you’ve just evolved a few more bells and whistles, but all of the ideas are in these simple systems that we can study.