Chromosomal curing drives prophage evolution and bacterial epidemiology

Many integrative mobile genetic elements (MGEs) are sensitive to RecA-DNA filaments, suggesting their activation may enable them to evade deletion through homologous recombination (HR). This was studied using pneumococcal prophage. Most pneumococci contained prophage that inhibited transformation-mediated HR through chromosomal modification. These included a commonly-targeted attB that reduced transformation by modifying the small cytoplasmic RNA. The prophage were almost universally regulated by C1-type or ImmAR-type systems. Representatives with either type were efficiently deleted by HR. Mutations that impaired a C1-regulated prophage increased this deletion rate, reflecting this element being activated by RecA-DNA filaments imported during transformation. ImmAR-regulated prophage instead responded to transient stimuli by excising as deletion-resistant pseudolysogens, with varying RecA sensitivity, gradually committing to lysing cells following longer-duration signals. These processes were modulated by interactions with the DNA-binding protein DprA. Therefore bacterial diversification though HR is impeded by MGEs that selfishly prevent themselves from being eliminated from the chromosome.