After infecting bacterial cells, bacteriophages must make a life-or-death decision; they either replicate and produce new phage particles, and in so doing kill their host (lytic cycle), or they can integrate their genome into that of the host, allowing host survival (lysogenic cycle). Depending on the environmental conditions, one or the other cycle may be more advantageous and, thus, deciding which one to trigger is important for phage population survival. When hosts are abundant, many phages undergo lytic cycles, increasing their population rapidly, but as host cell density declines, progeny phages are at risk of not finding prey to infect and must switch to lysogeny to avoid a collapse of the virus population.
In an article published in Nature today, Rotem Sorek and colleagues show that some bacteriophages can inform their peers of their population levels to guide lysis-lysogeny decisions through a system aptly dubbed arbitrium (which is Latin for “decision”). While looking for secreted communication molecules that might alert neighbouring bacteria of a bacteriophage infection, the Sorek group discovered a phage-encoded protein, AimP, similar to those implicated in bacterial quorum sensing. During infection, AimP is processed into a secreted 6 amino-acid communication peptide that is internalised by the bacterial oligopeptide permease transporter (OPP), which also takes up bacterial QS molecules. AimP is sensed by subsequent generations of the same phage; that is, progeny phages can “measure” the concentration of this peptide and lysogenize if it is sufficiently high. The study identifies the AimP receptor, AimR, which binds to the phage DNA as a dimer in the absence of the arbitrium peptide, activating the transcription of the lysogeny repressor AimX. Arbitirum binding to AimR induces its monomerization, inhibiting DNA binding and, thus, repressing AimX transcription. Although the mechanism whereby AimX negatively regulates lysogenic conversion remains to be elucidated, AimX mRNA expression is strongly repressed upon initial phage infection, its knockdown increases lysogeny and its ectopic expression can compensate for deletion of AimR in the induction of lysis.
The work focuses mainly on B. subtilis phages, although the authors find homologous systems in numerous other phages, highlighting their importance for phage survival. Importantly, they identify a wide diversity of AimP peptide sequences in the homologous arbitrium-like systems, and experimentally show that each AimP peptide affects only the population of the phage that produces it, implying a species-specific peptide communication code. As Alan Davidson eloquently puts it in the accompanying News & Views, which nicely puts these findings in the broader context of the field, “…these phages are speaking different languages, and want to convey crucial messages only to their own kind.”
This is the first viral extracellular communication system described, highlighting how complex and sophisticated even “simple” organisms really are. Phage genomes have many uncharacterized genes and it is tempting to speculate that if phages talk about lysis/lysogeny decisions, they may also talk about other things…
On a personal note, reading and having the opportunity to assist in the publication of such exciting work is what makes me love my job. This work is ground-breaking and quite frankly, very cool. I look forward to the next installments of the arbitrium saga!
You can listen to the corresponding author Rotem Sorek and me talking to reporter Noah Baker about the study in this week’s Nature podcast (from minute 16:58).