Mutation-induced infections of phage-plasmids

Phage-plasmids are extra-chromosomal elements that act both as plasmids and as phages, whose eco-evolutionary dynamics remain poorly constrained. Here, we show segregational drift and loss- of-function mutations play key roles in the infection dynamics of a cosmopolitan phage-plasmid, allowing it to create continuous productive infections in a population of marine Roseobacter. Recurrent loss-of-function mutations in the phage repressor that controls prophage induction led to constitutively lytic phage-plasmids that spread rapidly throughout the population. The entire phage-plasmid genome was packaged into virions, which were horizontally transferred by re-infecting lysogenized cells, leading to an increase in phage-plasmid copy number and to a heterozygous phage repressor locus within re-infected cells. While wild-type repressor variants prevented induction of phage-plasmids in a cell, the uneven apportionment of phage-plasmids after cell division (i.e., segregational drift) led to the production of offspring carrying only the constitutively lytic phage-plasmid, thus restarting the lysis-reinfection-segregation life-cycle. Mathematical models and experiments showed that these dynamics lead to a continuous productive infection of the bacterial population in which lytic and lysogenic phage-plasmids coexist. An analysis of marine bacterial genomes shows that the same plasmid backbone here described carries different phages in the environment and disseminates trans-continentally, suggesting that the phage-plasmid strategy is relevant and widespread in nature. Together, our study describes how the interplay between phage infection and plasmid genetics provide a unique eco-evolutionary strategy for phage-plasmids.