For the phage, coming out of hiding is irreversible, as the process destroys the original host. But if there’s a new crop of susceptible bacteria nearby, the benefits far outweigh the risk. So for VP882, monitoring the availability of prey—say, by encoding its own quorum sensing cipher—might be an incredibly effective strategy.

At first, the possibility seemed ludicrous to the researchers. But Silpe followed his hunch, and was amazed to find that the phage gene didn’t just look like VqmA—it listened like it, too. When Vibrios in its vicinity sent out DPO dispatches, VP882 took notice. And if the messages amassed, the phage jolted awake and broke loose from the cell.

Because more DPO means more bacteria—and, thus, more potential hosts—adding VqmA to its repertoire might be a way for a phage to time a mass exodus, Bassler explains. Though this idea awaits confirmation, Bassler thinks the virus might be using Vibrio’s own secret language against itself. It’s an “insidious and fantastic” tactic, she says.

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“This is remarkable,” says Asma Hatoum-Aslan, a microbiologist studying bacteria-phage interactions at the University of Alabama who did not contribute to the study. “This shows that this kind of phage, even in the host cell, is clearly not dormant. It’s listening. It’s still interacting with the environment on some level.”

The surprising crosstalk between such different entities also illuminates the widespread nature of communication—in even its simplest forms. “Viruses don’t carry much genetics around with them, but they actually have a lot of autonomy,” says Paul Turner, a phage biologist at Yale University who did not contribute to the study. Phages are dependent on cellular life to propagate, but by turning an ear to their hosts, he says, “they’re still encoded to decide their own fate.”

For Silpe and Bassler, this is only the beginning. This may be the first phage that’s officially recognized for learning the quorum sensing lingo, but the researchers think VP882 is unlikely to be alone.

Princeton University microbiologists Justin Silpe and Bonnie Bassler, who discovered a bacteriophage who can eavesdrop on bacterial conversations. Photo Credit: Denise Applewhite, Office of Communications, Princeton University

“Phages were discovered over a century ago,” says Rotem Sorek, a microbiologist who studies bacteriophages at the Weizmann Institute of Science in Israel but did not contribute to the study. “The foundations of microbiology came from phages. And still, after all these years, we are still finding very surprising and new features of phage biology.”

The researchers have already begun to brainstorm therapeutic applications of this unusual system. One potential avenue might be a riff on phage therapy, wherein bacteriophages can be deployed to selectively kill disease-causing bacteria. VP882 naturally targets bacteria of the Vibrio genus, including cholera-causing Vibrio cholerae. This phage could be engineered to function as something of a Trojan horse, Silpe says, delivering a molecular self-destruct button to dense populations of Vibrio without damaging, say, the important gut microbes that live within a human host. Turner compares the technique to “taking a scalpel and cutting something unwanted out of a complex community.”

Such a system would involve harnessing the power of a natural system derived from phage-microbe interactions—not unlike CRISPR, Turner says. “We’re figuring out what’s evolved in the microbial world and appreciating its elegance,” he explains. “But now we can also think about using these tools to solve human problems.”

Editor's Note, December 25, 2018: This article has been updated to clarify the role of Justin Silpe in the discovery of the quorum sensing molecule, DPO.

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