Viral Evasion of a Bacterial Suicide System by RNA–Based Molecular Mimicry Enables Infectious Altruism

Abortive infection, during which an infected bacterial cell commits altruistic suicide to destroy the replicating bacteriophage and protect the clonal population, can be mediated by toxin-antitoxin systems such as the Type III proteinâRNA toxin-antitoxin system, ToxIN. A flagellum-dependent bacteriophage of the Myoviridae, ΦTE, evolved rare mutants that âescapedâ ToxIN-mediated abortive infection within Pectobacterium atrosepticum. Wild-type ΦTE encoded a short sequence similar to the repetitive nucleotide sequence of the RNA antitoxin, ToxI, from ToxIN. The ΦTE escape mutants had expanded the number of these âpseudo-ToxIâ genetic repeats and, in one case, an escape phage had âhijackedâ ToxI from the plasmid-borne toxIN locus, through recombination. Expression of the pseudo-ToxI repeats during ΦTE infection allowed the phage to replicate, unaffected by ToxIN, through RNAâbased molecular mimicry. This is the first example of a non-coding RNA encoded by a phage that evolves by selective expansion and recombination to enable viral suppression of a defensive bacterial suicide system. Furthermore, the ΦTE escape phages had evolved enhanced capacity to transduce replicons expressing ToxIN, demonstrating virus-mediated horizontal transfer of genetic altruism. Bacteria are under constant attack by their viral parasites, bacteriophages, which outnumber bacteria by an estimated ten-to-one. The constant selection pressure from this predation promotes the evolution and dissemination of bacterial bacteriophage-resistance mechanisms. One family of protective systems causes the infected cell to undergo premature suicide, in an altruistic move that protects the clonal population of bacteria by blocking virus replication. We identified a means by which a bacteriophage counter-evolved to avoid one such system. This system relies on two components: a toxic part to kill the cell and an antidote that holds the toxin in check until required. The bacteriophage evolved sequences encoding mimics of the cellular antidote and expressed these mimics so that it could continue replicating without becoming a victim of the host's defensive system. Furthermore, this evolved bacteriophage was able to transfer the DNA encoding the defence system to a new bacterial host. In so doing, the evolved bacteriophage may have indirectly created populations of host cells inside which it could productively replicate, while also providing the host better protection from competing predators.