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 (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences microbiology bacteriology
- natural sciences biological sciences microbiology virology
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences genetics chromosomes
- natural sciences biological sciences genetics genomes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
ERC-COG - Consolidator Grant
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2018-COG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
69978 Tel Aviv
Israel
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