From time to time a paper appears with a particular scientific discovery that quickly captures the attention of the reading public. That’s what happened to a study published this year in Nature on January 18, by Rotem Sorek and his team from the Weizmann Institute of Science in Rehovot, Israel. It describes for the first time, that viruses which attack bacteria (phages) can ‘talk’ to each other using a chemical language. Moreover, it shows that this communication system is used by phages to decide what their infective plan would be. They could either infect a cell and kill it, releasing dozens of newly assembled viral particles- a process known as the lytic cycle- or alternatively they could choose to stay dormant in the host cell and wait until a better scenario appears in order to enter the lytic cycle again and continue replicating- a process known as the lysogenic cycle.
Communication within the ‘micro-world’ has already been seen in bacteria, a phenomenon famously known as quorum sensing, which refers to the ability of bacteria to sense information from other cells in the population when they reach a critical concentration- meaning a quorum. A beautiful example of quorum sensing, which also accounts for the first observation of this phenomenon back in the early 1970s, comes from a marine bacterium that glows in the dark, named Vibrio fischeri.What’s interesting about these bacteria is that they do not make light when they are alone; but when they grow to a certain number, all the bacteria within the community turn their light on simultaneously. But how can these bacteria tell the difference whether they are alone or they are in a community? What happens is that bacteria produce and secrete small molecules, known as autoinducers, into the environment. When bacteria are alone or in a very low cell density, the concentration of autoinducers is too low to be detected and they just flow away. But when bacteria grow and divide, the amount of autoinducers increases proportionally to the number of cells thus reaching a threshold level that allows the bacteria to sense it and, in response, to activate or repress target genes. In the case of the V. fischeri this response translates into producing light.
Intrigued by this communication system, Rotem Sorek’s team wanted to know if bacteria, specifically Bacillus subtilis, that have been previously infected by a phage, could use it to alert other bacteria of viral infection. To address this hypothesis, they infected a culture of B. subtilis with a phage called phi3T and saw that the virus killed a substantial fraction of the bacteria. But when they removed all bacteria and viruses from the culture medium by filtration and added a fresh batch of both bacteria and viruses to this ‘conditioned medium’, the picture changed: The virus now preferred to switch into a lysogenic cycle and to hide its genome within the bacteria, rather than kill it.
What was that mysterious compound in that ‘conditioned medium’ that could change the course of a new viral infection? Researchers surprisingly found that it was a molecule synthesized by the phages, that protected the bacterial cells from infection by that same phage. But why would viruses send a message for protecting bacteria? Isn’t their job the complete opposite? It sounds weird, but if you think about it, it makes a lot of sense. If the phage just keeps infecting and killing cells, eventually the virus will run out of host. If that happens, phages would limit their hosts destruction and stay mute till their hosts grow and multiply again. A clever way to preserve the chances for reproduction. The compound that guided lysis-lysogenic decision was identified as a peptide which was produced during phi3T infection and secreted from the bacteria. They named it ‘arbitrium’ after the Latin word for ‘decision’.
But how was this arbitrium message ‘heard’? When analyzing the phage’s genome, Sorek’s team found a putative intracellular receptor like the ones seen in quorum sensing system. By using Microscale thermophoresis, they showed that arbitrium binds to the receptor with high-affinity. A general model of this system is that initial bacterial infection with phi3T leads to a lytic cycle. At the same time, the arbitrium peptide is produced and secreted, accumulating in the medium after several cycles of infection. If a phage then infects a previously uninfected bacterium, the concentration of arbitrium, which is internalized into the bacterium by a membrane transporter, will be high enough for it to bind its intracellular receptor, a process that leads to the integration of the viral nucleic acid into the bacterial genome i.e. lysogeny.
This discovery could have tremendous implications. Just imagine if viruses infecting eukaryotes could communicate by this system. Imagine there was a molecule that could drive viruses into latency, wouldn’t it be a good therapy? Of course, there’s still a lot to be investigated.