Discovery and characterization of peptides that direct communication in phages and bacteria

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In every infection, temperate phages need to decide whether to replicate and lyse their host or to lysogenize and keep the host viable. As part of the first term of the current SPP2002 Priority Programme, we discovered that phages infecting Bacillus bacteria use a small-molecule communication system to coordinate lysis-lysogeny decisions (Erez et al., Nature 2017; Stokar-Avihail et al, Cell Host & Microbe 2019). During infection of its host cell, the phage produces a short (6aa-10aa) communication peptide that is produced by a µ-protein and released to the medium. In subsequent infections, progeny phages measure the concentration of this peptide and lysogenize if the concentration is sufficiently high. We termed this system the “arbitrium” system (“decision” in Latin). Our results showed that many phages harbor arbitrium-encoding µ-proteins and use them in order to communicate and coordinate infection decisions. However, so far all arbitrium homologs were found in prophages residing in bacterial genomes belonging to the taxonomic family Bacillaceae, and it is currently unknown whether phages infecting bacteria of other taxonomic groups also utilize peptide-based communication strategies for lysis/lysogeny decisions. In the current project we will attempt to discover additional, arbitrium-like systems in phages infecting non-bacillus species. As the discovery of the arbitrium system forms the first demonstration of actual communication between viruses, it represents a new paradigm in virology that may extend beyond the prokaryotic world. Understanding the diversity and constraints of phage communication systems will not only help us to assign function to hundreds of µ-proteins in bacterial and phage genomes, but may also set the stage for future such discoveries in viruses that infect higher organisms.As part of the first 3 years of SPP2002 we developed a general platform for the computational discovery and experimental validation of µ-proteins-based communication systems across thousands of genomes of interest. We showed that this platform could be used for discovery of new communication systems not only in phages, but also in bacteria. In the second major aim of this project, we plan to apply our platform on the thousands of Gram positive bacteria available in the public databases in attempt to massively uncover and validate new µ-proteins that direct bacterial communication.