Recent research from the University of Princeton has unveiled how viruses are triggered to activate and kill a cell. By utilizing high-resolution imaging, the researchers could monitor bacteriophages before and after introducing an artificial “kill signal” capturing the exact moment that bacteriophages attack.
Bacteriophages, the viruses that attack bacterial cells, do not immediately attack the cell once they land on the surface. Instead, they enter a state of lysogeny in which they deliver their genes into the cell and let it replicate alongside healthy cells. This replication continues until the bacteriophages receive a kill signal.
In the study, published in Nature, researchers found that bacteriophages can “eavesdrop” on the communications between cells. This allows them to silently replicate until a problematic chemical signal is detected before they kill the cell. Previously, scientists believed that in polylysogeny, the viruses would compete for the bacterium resources upon receiving a trigger and the fastest would win by out-competing other viral particles. However, by utilizing high-resolution imaging and fluorescent tagging of the bacteriophage genes, the researchers discovered that there was no clear winner. Some bacteria glowed with one color, while others glowed with another color or even a blend of colors by producing both phages simultaneously.
"That was a really exciting day," said Grace Johnson - a postdoctoral research associate at Princeton University. "I could see the different cells undertaking all the possible phage production combinations—inducing one of the phages, inducing another, inducing both. And some of the cells were not inducing either of the phages."
Despite not fully understanding what signals individual phages respond to in nature, the team developed artificial chemical triggers to target each phage. When exposing the polylysogenic cells to the trigger, only the phage that responded to the artificial trigger activated while the others remained in “chill” mode.
"Yes, here, we discovered the functions of a few phage genes, and we showed that their jobs are to enable this completely unexpected chill-kill switch and that the switch dictates which phage wins during phage-phage warfare. That discovery suggests there remain potentially even more exciting processes left to find," said Bonnie Bassler, a Princeton biologist.