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Biologists Engineer An Eavesdropping Virus Into A Bacterial Assassin

“When bacteria talk, Bonnie Bassler listens. She just never figured that viruses were listening, too.” – The Atlantic

A phage is a type of virus that preys on and attacks bacteria. A team of scientists from Princeton have discovered that some phages actually “listen” to the conversations that take place between bacteria to identify the ideal time to strike. The one in specific that they found to be eavesdropping is called VP882. They believe this discovery could be useful in the battle against antibiotic resistance.

This is a completely new perspective on the dynamic relationship between viruses and their hosts. This recent study tells us for the first time… “that when a phage is in the lysogenic [stay] state, it is not ‘fast asleep’, but rather catnapping, with one eye open and ears alert, ready to respond when it ‘hears’ signals that cells are getting ready to respond to changes in their environment,” according to Graham Hatfull, the Eberly Family Professor of Biotechnology at the University of Pittsburgh, who was not involved in this research.

Phage therapy is a known medical strategy in which they target a bacterial disease with a phage. Therefore, VP882 is not the first virus used as an antimicrobial treatment but it is the first phage that uses eavesdropping to know when it is optimal to kill its targets.

“It’s brilliant and insidious!” researcher Bonnie Bassler of the study said in a press release. “It’s also the first known example of such radically different organisms listening to one another’s communications.”

Bonnie Bassler and Justin Silpe, Department of Molecular Biology, Princeton University
Images courtesy of Bonnie Bassler and Justin Silpe, Department of Molecular Biology, Princeton University

They have long known that bacteria can communicate through the release of molecules. This new research builds onto that. There’s a paper published in the journal Cell where Princeton researchers describe this. It explains how the mechanism works: there’s a virus called VP882, which “listens” for those molecules in order to know when there are enough bacteria around to justify attacking, a process that involves creating many replicas of itself. They have to eavesdrop because if there aren’t enough bacteria around, the VP882 virus and its replicas will all die after the attack.

“A virus can only ever make one decision,” Bassler said, “Stay in the host or kill the host. That is, either remain under the radar inside its host or activate the kill sequence that creates hundreds or thousands of offspring that burst out, killing the current host and launching themselves toward new hosts.”

Graduate student Justin Silpe was able to re-engineer the VP882 virus so that he would provide the commanding sensory input, rather than the communication molecule that naturally set it off. By doing so he got the virus to kill on his demand.

E. coli bacteria infected with eavesdropping virus
E. coli bacteria infected with eavesdropping virus
“These E. coli bacteria harbor proteins from the eavesdropping virus. One of the viral proteins has been tagged with a red marker. When the virus is in the “stay” mode (left), the bacteria grow and the red protein is spread throughout each cell. When the virus overhears that its hosts have achieved a quorum (right), the kill-stay decision protein is flipped to “kill” mode. A second viral protein binds the red protein and sends it to the cell poles (yellow dots). All the cells in the right panel will soon die.” – Bonnie Bassler and Justin Silpe, Department of Molecular Biology, Princeton University

“The bugs are getting bugged,” she said with a laugh. “Plus, Justin’s work shows that these quorum-sensing molecules are conveying information across kingdom boundaries. Viruses are not in the same kingdom as bacteria — in fact, they are not in any kingdom, because they are not technically alive. But for such radically different organisms to be able to detect and interpret each other’s signals is simply mind-boggling.”

Silpe said he was inspired by Bassler’s earlier work in the lab – her research on bacterial communication. It drew him to go work with her. “Communication seems like such an evolved trait,” he said. “To hear that bacteria can do it — her discovery — it was just mind-blowing that organisms you think of as so primitive could actually be capable of communication. And viruses are even simpler than bacteria. The one I studied, for example, only has about 70 genes. It’s really remarkable that it devotes one of those genes to quorum sensing. Communication is clearly not something higher organisms created.”

“These are inanimate, non-living viruses. There’s something beautiful about how ancient communication is.” – Bassler

Furthermore, this virus holds enormous promise as a therapeutic tool because it does not act like a typical virus. VP882 itself is unique in that it can infect multiple types of cells. Normally this is not the case. A virus can only attack one specific type of cell. For example, the flu attacks respiratory and HIV attacks the immune system. But in tests, Silpe manages to get VP882 to attack cholera, salmonella, and E. coli — three very different types of bacteria.

Now that they know they can turn a least one phage into an assassin, they might be able to find a way to use it against the antibiotic-resistant bacteria currently threatening global health. They are very optimistic about the utility of this re-engineered virus for antibiotic-resistant bacteria, which is clearly a major global health threat. These viral assassins might be the way to slow down the emergence of antibiotic-resistant strains.

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