Researchers at Princeton University have found a virus called VP882 that can eavesdrop on the communications between bacteria. The virus senses a bacterial signaling molecule. Molecular biologist Bonnie Bassler and graduate candidate Justin Silpe then altered VP882 so it would attack and kill pathogens after detecting something the researchers directed it to sense. Their work has been reported in Cell.
"The idea that a virus is detecting a molecule that bacteria use for communication -- that is brand-new," said Bassler, the Squibb Professor of Molecular Biology and a Howard Hughes Medical Institute Investigator. "Justin found this first naturally occurring case, and then he re-engineered that virus so that he can provide any sensory input he chooses, rather than the communication molecule, and then the virus kills on demand."
The virus can make one choice, explained Bassler: it can remain inside the host, where it stays under the radar, or, kill it by generating tons of viral particles that then burst out of the host cell. The option to release viral particles, and destroy the host, comes with a risk, however. "If there are no other hosts nearby, then the virus and all its kin just died," she noted.
VP882 can mitigate that risk by listening in on bacterial communication; when the microbes are signaling that they're in a crowd, the virus has a good chance of finding a new host when it kills the one it has. "It's brilliant and insidious!" exclaimed Bassler.
Bassler had already found that bacteria are able to communicate with one another, establishing a quorum when a bacterial community has to act together. It was a surprise for her to find that viruses can eavesdrop on the microbial quorum-sensing communication.
"The bugs are getting bugged," she joked. "Plus, Justin's work shows that these quorum-sensing molecules are conveying information across kingdom boundaries." Viruses are not in any kingdom used to classify biological life, and many would argue that they are not technically alive. They are able to understand the signaling used by bacteria, which was mind-boggling for Bassler to discover. Silpe began to look for more evidence of organisms listening in on one another across kingdoms and found more.
After identifying VP882, the researchers turned their attention toward engineering it so it would kill when directed. The idea of using viruses to target bacterial pathogens is not new; it’s called phage therapy when used as a medical treatment. But this is the first instance of using cross-kingdom communication to find the best way for a virus to kill its targets.
This virus has a lot of potential because it can target many different kinds of cells. Many viruses can only zero in on one cell type; HIV targets specific immune cells, while the flu targets lungs cells, for example. But VP882 can be hosted by many cell types. After testing three unrelated bacteria, salmonella, E. coli, and Vibrio cholera, Silpe found that all were susceptible to VP882. Many more bacteria may also be vulnerable to its eavesdropping abilities.
"He just started a brand-new field," Bassler said. "The idea that there's only one example of this cross-domain communication made no sense to us. Justin discovered the first case, and then, with his discovery in hand, he went looking more deeply, and he found a whole set of viruses that harbor similar capabilities. They may not all be listening in to this quorum-sensing information, but it is clear that these viruses can listen in to their hosts' information and then use that information to kill them."
Bassler is featured discussing quorum sensing in the video.