Quorum sensing was already a revolutionary concept. As Bassler uncovered its details over decades, she and others were shocked to realize that supposedly simple organisms such as bacteria could communicate and coordinate. But viruses are even simpler. They’re not even technically alive! They’re entirely different entities from bacteria, yet they are intercepting and interpreting the same molecular messages. It’s like a rock eavesdropping on a bird.
The seeds of this discovery were planted a few years ago, when Bassler’s team identified a new kind of quorum-sensing system in Vibrio cholerae, the bacterium that causes cholera. It secretes a signaling molecule called DPO, which it detects using a protein called VqmA.
When the bacteria start to infect a host, there aren’t many of them around, and the DPO signals they produce drift off into the ether. But as their numbers swell, the signals become more concentrated and start landing on the VqmA detectors. When this happens, it triggers a sequence of genes that reprogram the bacteria, turning off their ability to infect and turning on their ability to disperse. This is partly why “cholera is such an insidious disease,” says Bassler. Through quorum sensing, Vibrio cholerae can wait until the time is right, before “getting out of the host by the gazillions to infect the next host.”
By searching through online databases, Silpe showed that many closely related Vibrio bacteria also have detectors that resemble VqmA. But so, apparently, did a virus—a phage called VP882, which some Taiwanese researchers had found from a marine Vibrio a decade ago. Was that a random coincidence? A mistake in the database? Or, as Silpe suggested, could the virus somehow be tapping into the messages of its hosts? “I thought, We’re going to waste a lot of time on this, because it’s a crazy mistake,” says Bassler, cheerfully. “But that’s what we do.”
The researchers who found the VP882 virus had retired, but not before putting a sample of the host bacteria in a repository. It took six months for Silpe to track down that precious sample, and fortunately, those bacteria still had some virus inside them.
Through careful experiments, Silpe showed that his hunch was right: The virus’s version of VqmA can indeed detect the same DPO signals that the bacteria release. And when it does, it prompts the virus, which usually lies harmlessly in wait, to start killing its host. “There’s a funny logic to it,” says Bassler. “At high densities, cholera, a parasite, wants to leave its host and get into another host. And at high densities, the virus, a parasite of a parasite, wants to leave its host and get into another host. They’re doing the same thing [using the same signal molecule].”
The virus isn’t just eavesdropping either. Remember how the cholera bacterium uses its VqmA detector to shift from infection to dispersal. Silpe found that the virus’s version of VqmA can launch the same genetic program, forcing its bacterial host to disperse. “The phage, while it’s preparing to kill cholera, is also messing with hundreds of bacterial genes,” Bassler says. Perhaps that’s all part of the same strategy: The phage not only ensures that its progeny have plenty of hosts to infect, but also ensures that those hosts spread far and wide.