Descripción del proyecto
Cooperación entre bacteriófagos y hospedador bacterianos durante las infecciones
Los bacteriófagos son virus parásitos que utilizan las células bacterianas para propagarse y desempeñan un papel en la evolución bacteriana. Los bacteriófagos líticos entran en un ciclo productivo tras la infección, en el que generan y liberan viriones a través de la lisis, mientras que los bacteriófagos lisogénicos se propagan sin activar el ciclo lítico. Su genoma se integra en el cromosoma bacteriano como probacteriófago y se replica con el cromosoma del hospedador, pero puede pasar a la producción lítica en condiciones de estrés. En un estudio reciente se demostró que el probacteriófago infeccioso promueve la virulencia del hospedador bacteriano «Listeria monocytogenes» a través de un comportamiento adaptativo y depende de factores reguladores derivados de los restos del probacteriófago en el genoma bacteriano. El equipo del proyecto CoPathoPhage, financiado con fondos europeos, investigará los mecanismos de regulación cruzada y de cooperación de los elementos bacteriófago, lo que proporcionará nuevos conocimientos sobre la coexistencia entre bacterias y bacteriófagos.
Objetivo
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.
Ámbito científico
Programa(s)
Régimen de financiación
ERC-COG - Consolidator GrantInstitución de acogida
69978 Tel Aviv
Israel