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Interference with defensive responses in pathogenic communities at the host interface: A modelling approach towards an integrated strategy for Salmonella control in chickens.

Bacteria in the gut live in dense and genetically diverse communities, in which they strongly compete with each other for resources and space. A key corollary of the importance of competition is that it should strongly shape bacterial regulatory networks. Indeed, natural selection should favor cells that can detect and respond appropriately to the presence of competing strains. We hypothesize that these defensive responses to competition are at the basis of an enhanced persistence and virulence of pathogens in the gut. Support is provided by our initial observation that enteric pathogens such as Salmonella Typhimurium enhance their bacterial biomass, antimicrobial tolerance and epithelial invasion as a response to competitors. Recent findings indicate that Salmonella as part of such defensive response- can also exploit the host immune system to fight competitors. In this project we will combine in vitro experiments and sophisticated individual-based models to unravel how Salmonella integrates different candidate molecular systems for detecting competitors in the chicken gut in order to induce the best defensive response possible, i.e., (i) Quorum Sensing systems, which allow bacteria to sample the density of cells of their own genotype and/or other genotypes and (ii) stress response systems, which directly sense harm (i.e., nutrient limitation or cell damage) caused by other cells. We will then investigate how the induced responses alter the interaction of Salmonella with the chicken host immune system to exploit it to its own benefit. To this end we will introduce isolated host components and cecal explants to the in vitro models and finally use a chicken animal model. The acquired knowledge will be applied to design an integrated anti-Salmonella strategy for poultry flocks that includes (a) optimal probiotics that compete with Salmonella, (b) phytobiotics that interfere with harmful defensive responses in Salmonella and (c) immune modulators that boost host defence mechanisms and overcome Salmonella tolerance.

Date:19 Jun 2019 →  Today
Keywords:Bacteria-Host Interactions
Disciplines:Animal immunology
Project type:PhD project