Identification and characterization of competition-factors of commensal E. coli and their role in inhibition of enteropathogens in the inflamed intestine

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Gastrointestinal infections are a major global health problem claiming 1.8 million lives per year according to the WHO. The commensal microflora, populating the intestine to high levels, con-tributes to protection against these infections. Inflammation, induced by enteric pathogens des-tabilizes the normal microbiota by so far poorly understood mechanisms and leads to pathogen overgrowth. So far, it has been assumed that only pathogens (i.e. Salmonella enterica spp.I serovar Typhimurium) can benefit from intestinal inflammation. However, we have recently ob-served that certain E. coli strains (i.e. commensal mouse isolate E. coli 8178) in contrast to oth-ers (i.e. E. coli Nissle) can out-compete Salmonella Typhimurium in a mouse colitis model. In the proposed project we plan to investigate the molecular mechanisms of competitive E. coli overgrowth and pathogen suppression in the inflamed gut. We aim at identifying traits that con-tribute to the competitive phenotype of E. coli 8178 (= 'competition-genes') but are absent in E. coli Nissle by using two independent genetic screening approaches. We will analyze the distri-bution of 'competition-genes' within the E. coli pangenome and address their regulation in re-sponse to in vivo stimuli. The results will enhance our understanding of the role of competitive E. coli in enteropathogen infection and may be exploited for the improvement of probiotics in the future.