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Studying Pathogen Phage Host Interactions

Final Report Summary - PATHOPHAGEHOST (Studying Pathogen Phage Host Interactions)

The human bacterial pathogen Listeria monocytogenes strain 10403S harbors a prophage within its genome, which is known to reproduce by both the lytic and lysogenic cycles. We have shown that this prophage acquired an unusual behavior when L. monocytogenes infects mammalian cells. During macrophage cells infection the prophage, which is inserted within the comK gene, excises its genome leaving an intact comK gene that is necessary to facilitate bacterial phagosomal escape. Even though phage excision occurs, it does not lead to generation of progeny virions and bacterial lysis, suggesting that the prophage cooperates with its host to promote successful mammalian infection. We termed this novel phage behavior active lysogeny, representing cases where prophages serve as regulators of bacterial gene expression.
In this research project we investigated phage and bacterial regulatory mechanisms that promote active lysogeny. By characterizing the three life cycles of the phage: lytic, lysogenic and active lysogenic, we uncovered specific phage mediated regulatory adaptations to the complex mammalian environment. The transcriptional behavior of the prophage during active lysogeny demonstrated a specific downregulation of the late lytic genes.
We further found that Listeria monocytogenes strain 10403S harbors two phage elements in its chromosome, both of which can trigger bacterial lysis under stress: an active prophage and a locus encoding phage tail-like bacteriocins. We show that the two phage elements are co-regulated, with the bacteriocin locus controlling the induction of the prophage and thus its activity as a virulence-associated molecular switch. Overall, our studies strengthen the premise that L. monocytogenes and its cohabiting phage elements co-evolved to cooperate during mammalian infection.