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

肠道微生物群与其宿主的共同进化导致了互惠互利的状态。除了有助于宿主营养、生理和粘膜免疫外，肠道微生物群还保护宿主免受肠道感染，这一功能被称为定植抗性。通过表达毒力和适应性因子，肠道病原体可以利用宿主的结构和信号传导途径来破坏免疫系统的特定功能。虽然在过去的几十年中已经详细研究了宿主-病原体相互作用，但微生物群在这种相互作用中的作用在很大程度上是难以捉摸的，并且肠道病原体、肠道微生物群和宿主之间的三边相互作用还没有得到很好的理解。在此，我们解决肠道小肠结肠炎耶尔森氏菌（叶）的毒力因子是否以及如何影响这种相互关系，以及是否以及如何微生物群的特定成分可能被用来干扰叶致病性。为此，我们将使用Ye野生型和等基因突变株，实验小鼠耶尔森氏菌感染模型，包括无菌（GF）和gnotobiotic小鼠以及宏基因组分析，以解决特定的假设。这些研究的结果将为Ye，肠道微生物群和粘膜免疫系统之间复杂的相互作用提供新的见解，并可能导致治疗肠道感染的新策略。

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.