This level of complexity is another example, Bassler says, of something she and her colleagues could not have imagined a decade ago. "How could I have been so slow?" she says. "Now it seems obvious to me that it had to work like this."

Bassler decoded the structure of the AI-2 molecule and has shown what happens inside bacteria when they detect these chemical signals—how their communication changes the bacteria's behavior. "She's shown that bacteria have much more sophisticated information-processing systems than we imagined," says Harvard's Losick.

Researchers elsewhere have now found Bassler's second signal in hundreds of other bacterial species. But there is an unsolved problem regarding the determination of "other." The molecules they've been studying identify an organism as self or other but do not tell who that other organism is or whether it's an ally or a threat. Bacteria must have additional signals—other molecules—to distinguish between species. "There are probably a lot of them," says Bassler. Nobody yet knows how many.

One potential application of Bassler's work is an entirely new kind of antibiotic. At present, most antibiotics are poisons of one sort or another—they kill bacteria. But here, she says, "the idea is that instead of killing bacteria, you make molecules that lead to behavior modification."

When infectious bacteria invade human beings, they generally do not start to make toxins right away. That would only draw the attention of the immune system, which would blast them out of existence. They wait until their numbers have increased, and, using quorum sensing, when they detect the appropriate threshold population, they act together to launch a major attack, making it far more likely they can overpower the immune system's defenses. An anti-quorum-sensing drug, by preventing this process from occurring, should avert or even cure infections. It might also be possible to make molecules that enhance quorum sensing in the commensal bacteria, described by Bassler as "those harmless gobs of everyday bacteria that live in and on us," thereby allowing them to keep out invading infectious microbes.

And then comes the next leap, as Bassler sees it. Over billions of years of evolution, bacteria have undoubtedly learned to modify quorum sensing in competing bacteria. Therefore, the drugs that researchers seek probably already exist in nature. It's just a question of finding them. She's interested in basic research—not drug development—but her work could point drug makers to these naturally occurring medicines.

		Most bacteria want to get into the body, reproduce, and stay forever. They multiply until they have reached sufficient numbers to attack, and then, sensing that they have a quorum, launch the attack. But Vibrio cholerae, the cause of the devastating infection known as cholera, is different. It lives in contaminated drinking water, which is how it typically enters the body. Once there, it attaches itself to the intestine and begins to manufacture the toxins that cause the illness, even before its numbers have significantly risen. It is virulent from the start. And when it reaches a particular population threshold—which it measures through quorum sensing—it switches off its virulence genes. Then V. cholerae produces an enzyme that clips many of its number off the intestinal walls. By that time, enough toxin has been produced to cause diarrhea, which washes the newly freed bacteria out of the body. Some of them wind up in puddles and rivers, and eventually in drinking water. V. cholerae's behavior clearly differs from that of most other pathogenic bacteria. It wants to stay in the body for only a short time—to reproduce far faster and more efficiently than it could in a pool of standing water—and then escape in large numbers to infect more hosts. Although with other infections the idea is to develop a drug that disrupts quorum sensing—so that the bacteria don't initiate virulence—with V. cholerae the opposite strategy applies, says Bassler. "Here, the drug is the autoinducer itself, or a similar molecule that would hasten quorum sensing—and terminate virulence prematurely. We want the Vibrio cholerae to let go before they've increased their numbers and produced a lot of toxin." In some of their most recent research efforts, Bassler and her colleagues have purified, identified, and synthesized the V. cholerae autoinducer. And they've shown that if they add the synthetic molecule to V. cholerae it turns off virulence. The next step is to try that experiment in mice. If the scientists can curtail virulence in mice, they could have the makings of a powerful new cholera drug. —P.R.

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