Interaction between Yersinia enterocolitica, the intestinal microbiota, and the host: from molecular analysis to therapeutic intervention

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Co-evolution of the intestinal microbiota with its host has resulted in a state of mutual benefit. Besides contributing to host nutrition, physiology and mucosal immunity, the intestinal microbiota protects the host from enteric infections, a function designated as colonization resistance. By expression of virulence and fitness factors, enteric pathogens may exploit structures and signaling pathways of the host in order to subvert specific functions of the immune system. While hostpathogen interactions have been studied in detail during the past decades, the role of the microbiota in this interaction is largely elusive, and the trilateral interaction between enteric pathogens, the intestinal microbiota and the host is not well understood. Herein we address whether and how virulence factors of enteric Yersinia enterocolitica (Ye) affect this interrelationship, and whether and how specific components of the microbiota might be used to interfere with Ye pathogenicity. To this end, we will be using Ye wildtype and isogenic mutant strains, an experimental mouse Yersinia infection model including germ-free (GF) and gnotobiotic mice as well as metagenomic analyses to address the specific hypotheses. The results of these investigations will provide new insights into the intricate interaction between Ye, the intestinal microbiota and the mucosal immune system, and might result in novel strategies for treatment of enteric infections.