Researchers at Princeton University have described* a bacteriophage, VP882, that can intercept and interpret bacterial communication signals and are looking for a way to use this phenomenon to improve the effectiveness of phage therapy for intestinal infections.

A real sensation in microbiology was the discovery that viruses can detect and respond to the substances bacteria use for communication. This discovery also laid the foundation for the creation of a unique system for controlling bacteriophages using artificial chemical signals.

A bacteriophage has two options in its life: it can remain dormant within its host bacteria (the lysogenic cycle) or it can kill them (the lytic cycle). In the latter case, thousands of new phage particles are released from the bacteria in search of new hosts. If the desired bacteria are not nearby, they gradually die. The VP882 phage has found a way to reduce the risk of this unfortunate scenario: it waits until the bacteria "announce" their abundance before initiating the lytic cycle. This dramatically increases the chances of the phage's progeny finding a host.

The authors of the study explain that when a bacteriophage is in a lysogenic state, it is generally believed to not be "sleeping" but rather waiting, as if in ambush, for certain signals. These signals in bacteria were discovered 25 years ago and are called "quorum sensing." They ensure the coordination of bacterial activities: division, biofilm formation, exopolysaccharide production, cell aggregation, and so on. But until now, no one could imagine that viruses could intercept and interpret these signals.

Conventional bacteriophages have been used to treat bacterial infections for decades, but VP882 is the first phage discovered that "chooses" the best moment to kill—when the bacteria it's specifically targeting are abundant. Researchers were confident that this phenomenon couldn't be unique to one type of bacteriophage and quickly discovered similar properties in a number of other phages.

Having studied the molecular mechanisms used by VP882, the scientists reprogrammed it to initiate the lytic cycle in response to chemical signals specified by the researcher. Furthermore, the authors of the study argue that phage VP882, unlike other viruses, is not highly specific and can attack a variety of unrelated bacterial species. For example, in an experiment, VP882, on command from the researchers, destroyed pathogens associated with intestinal infections: Vibrio cholerae, Salmonella, and E. coli.

The ability to genetically modify bacteriophages so that they switch from the lysogenic to the lytic cycle in response to a specific chemical “command” could significantly expand the capabilities of phage therapy.

*Silpe JE and Bassler BL. A Host-Produced Quorum-Sensing Autoinducer Controls a Phage Lysis-Lysogeny Decision // Cell, Published: December 13, 2018. DOI: 10.1016 / j.cell.2018.10.059