Project description
Bacteriophage–bacterial host cooperation during infection
Bacteriophages (Bps) are parasites that use bacterial cells for propagation and play a role in bacterial evolution. Lytic Bps enter a productive cycle after infection, generating and releasing virions via lysis; lysogenic Bps propagate without activating the lytic cycle. Their genome integrates into the bacterial chromosome as a prophage and replicates with the host chromosome, but it can switch into lytic production under stressful conditions. A recent study demonstrated that the infective prophage promotes the virulence of bacterial host Listeria monocytogenes via adaptive behaviour and depends on regulatory factors derived from prophage remnants in the bacterial genome. The EU-funded CoPathoPhage project will investigate cross-regulatory and cooperative mechanisms of phage elements, providing novel insights into bacteria–phage coexistence.
Objective
Most bacterial pathogens are lysogens, namely carry DNA of active phages within their genome, referred to as prophages. While these prophages have the potential to turn under stress into infective viruses which kill their host bacterium in a matter of minutes, it is unclear how pathogens manage to survive this internal threat under the stresses imposed by their invasion into mammalian cells. In the proposed project, we will study the hypothesis that a complex bacteria-phage cooperative adaptation supports virulence during mammalian infection while preventing inadvertent killing by phages. Several years ago, we uncovered a novel pathogen-phage interaction, in which an infective prophage promotes the virulence of its host, the bacterial pathogen Listeria monocytogenes (Lm), via adaptive behaviour. More recently, we discovered that the prophage, though fully infective, is non-autonomous- completely dependent on regulatory factors derived from inactive prophage remnants that reside in the Lm chromosome. These findings lead us to propose that the intimate cross-regulatory interactions between all phage elements within the genome (infective and remnant), are crucial in promoting bacteria-phage patho-adaptive behaviours in the mammalian niche and thereby bacterial virulence. In the proposed project, we will investigate specific cross-regulatory and cooperative mechanisms of all the phage elements, study the domestication of phage remnant-derived regulatory factors, and examine the hypothesis that they collectively form an auxiliary phage-control system that tempers infective phages. Finally, we will examine the premise that the mammalian niche drives the evolution of temperate phages into patho-adaptive phages, and that phages that lack this adaptation may kill host pathogens during infection. This work is expected to provide novel insights into bacteria-phage coexistence in mammalian environments and to facilitate the development of innovative phage therapy strategies.
Fields of science
Programme(s)
Funding Scheme
ERC-COG - Consolidator GrantHost institution
69978 Tel Aviv
Israel