Coordination of cohabiting phage elements supports bacteria\u2013phage cooperation

Tal Argov,Lev Rabinovich,Anna Pasechnek,Anat A Herskovits,Nadejda Sigal,Ilya Borovok,Olga Stadnyuk,Shai Ran Sapir,Gil Azulay

doi:10.1038/s41467-019-13296-x

Abstract

Bacterial pathogens often carry multiple prophages and other phage-derived elements within their genome, some of which can produce viral particles in response to stress. Listeria monocytogenes 10403S harbors two phage elements in its chromosome, both of which can trigger bacterial lysis under stress: an active prophage (ϕ10403S) that promotes the virulence of its host and can produce infective virions, and a locus encoding phage tail-like bacteriocins. Here, 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. More specifically, a metalloprotease encoded in the bacteriocin locus is upregulated in response to stress and acts as an anti-repressor for CI-like repressors encoded in each phage element. Our results provide molecular insight into the phenomenon of polylysogeny and its intricate adaptation to complex environments.

Highlights

Bacterial pathogens often carry multiple prophages and other phage-derived elements within their genome, some of which can produce viral particles in response to stress
We examined the capacity of each hol-lys module to trigger bacterial lysis in response to treatment with mitomycin C (MC), a DNA damaging agent known to trigger the SOS response
The Listeria monocytogenes (Lm) 10403S monocins could kill a variety of Listeria strains and species, e.g., Lm Scott A, L. innocua CLIP 74915, and L. welshimeri DSM 20650, an activity that was independent of φ10403S-prophage (Fig. 1c)

Summary

Introduction

Bacterial pathogens often carry multiple prophages and other phage-derived elements within their genome, some of which can produce viral particles in response to stress. The prophage excision was strongly induced when the bacteria were located within the macrophage phagosomes, but in contrast to classic phage induction, this did not lead to the production of progeny virions and bacterial lysis[12] These observations demonstrated an intriguing adaptive (cooperative) behavior of the prophage to the intracellular life style of its host, where it apparently could serve as a molecular switch that regulates bacterial gene expression to promote virulence. We termed this type of phage behaviour active lysogeny, to describe cases where prophages function as active regulatory DNA elements without triggering their lytic cycle[13,14]. Our findings reveal an inter-phage cross-regulatory interaction that coordinates co-habiting lytic phage elements, and promotes their cooperation with the host in complex environments, such as within the mammalian niche

Methods

Results

Conclusion