Prophage Excision Activates Listeria Competence Genes that Promote Phagosomal Escape and Virulence

The DNA uptake competence (Com) system of the intracellular bacterial pathogen Listeria monocytogenes is considered nonfunctional. There are no known conditions for DNA transformation, and the Com master activator gene, comK, is interrupted by a temperate prophage. Here, we show that the L. monocytogenes Com system is required during infection to promote bacterial escape from macrophage phagosomes in a manner that is independent of DNA uptake. Further, we find that regulation of the Com system relies on the formation of a functional comK gene via prophage excision. Prophage excision is specifically induced during intracellular growth, primarily within phagosomes, yet, in contrast to classic prophage induction, progeny virions are not produced. This study presents the characterization of an active prophage that serves as a genetic switch to modulate the virulence of its bacterial host in the course of infection. [Display omitted] ► Listeria monocytogenes prophage serves as a genetic switch that modulates virulence ► Prophage genome excision is triggered upon bacterial phagocytosis ► Prophage excision results in an intact and functional comK gene ► ComK activates the competence apparatus, promoting phagosomal escape Competence genes in most bacteria facilitate the uptake of external DNA, but it turns out that Listeria activates these genes only inside a host cell to promote escape from phagosomes.