Viruses are tiny, and bacteria are huge in comparison, but they have a lot of things in common. The nasty ones try to drive humanity and other living creatures crazy, as we see in the current pandemic. There are beneficial bacteria such as those in the microbiome (digestive system), and there are even beneficial viruses called bacteriophages (“phages” for short) that attacks bacteria. 

Viruses and bacteria actually communicate with each other, just like humans, although without smartphones or email. Researchers at Tel Aviv University (TAU) have discovered a new mechanism for communication between viruses and bacteria. As antibiotics are increasingly meeting resistance from bacteria and unable to fight many infectious effectively, this new knowledge is very important.

Their new study, led by Prof. Avigdor Eldar of TAU’s Shmunis School of Biomedicine and Cancer Research, together with his students and partners from the Weizmann Institute of Science in Rehovot, has found that, just like humans with game theory, phages weigh all options and finally make an informed decision – whether the time has come to exit the dormant state and attack their bacterial host.

The study has just been published in the prestigious journal Nature Microbiology under the title “Dormant phages communicate via arbitrium to control exit from lysogeny.” 

Many phages can exist in one of two states: active (lysis), in which the phages attack and destroy bacteria, or dormant, in which they remain passive within the bacteria, replicating themselves but doing no damage (lysogeny). Phages of this type must decide whether to be active or dormant every time they infect a new host. If they decide to be dormant for a time, they must also decide when to “wake up” and attack. As in all dilemmas, it’s important to base the decision upon solid, reliable information.

According to the researchers, it has been assumed for some time that a phage bases its decision to exit the dormant state on information regarding condition of its bacterial host. When the host shows signs of substantial DNA damage (death throes, so to speak), it’s in the phage’s interest to leave it and try to infect other bacteria. 

The new study discovered an additional mechanism of communication between bacteria and phages – apparently, some phage families have developed a more complex decisionmaking strategy, a kind of “phage game theory” in which the phage receives information not only from its own host but also from neighboring bacteria.

“When a phage is dormant within a bacterial cell, it forces its host to constantly produce small communication molecules called arbitrium, to which the phage listens via a special receptor.” Eldar explained. “Thus, the presence of high levels of these molecules indicates that neighboring bacteria also contain phages. When this happens, even if its own host exhibits DNA damage, the phage refrains from becoming active. Since every bacterium can host only one dormant phage, the bacteriophage makes an informed decision that it’s better to let the host try to repair itself than to ‘betray’ it, since all neighboring bacteria are already taken.”

Eldar and his team used a variety of genetic and biomolecular methods to track the biochemical communication signals passing between the bacteria and phages. In a previous study. they used a fluorescent marker to show that communication methods used by phages and a large family of similar communication systems (know generally as ‘quorum sensing’) are used only to get signals from close neighbors. “Essentially, the bacteria have developed two separate communication systems – one for long-range communication, and the other for short distances only, used to sense the state of their immediate neighbors,” noted Eldar. “In the phage’s case, it controls communication and is interested only in knowing whether its close neighbors that it might easily infect are already occupied.”

“Several years ago, Prof. Rotem Sorek and his team at the Weizmann Institute identified communication between phages for the first time. Such systems had been known to exist between other molecular parasites hosted by bacteria called plasmids. Our new discovery is the fact that phages use communication even in their dormant state. We have identified components critical for understanding how phages combine information about their host’s condition with information about their neighbors. This is one more important step on the way to deciphering the communication and ‘behavioral economics’ of viruses. Phages have an excellent ability to process information and make the right decision to ensure optimal survival. It will be interesting to see whether viruses residing in more complex organisms but facing similar decisions have also developed comparable systems of communication.”