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

肠道微生物区系与宿主的共同进化导致了一种互惠互利的状态。除了有助于宿主的营养、生理和粘膜免疫外，肠道微生物区系还保护宿主免受肠道感染，这一功能被称为定植抵抗。肠道病原体通过表达毒力和适应因子，可以利用宿主的结构和信号通路来破坏免疫系统的特定功能。虽然在过去的几十年里，人们对寄主病原体的相互作用进行了详细的研究，但微生物区系在这种相互作用中的作用在很大程度上是难以捉摸的，肠道病原体、肠道微生物区系和宿主之间的三方相互作用也不是很清楚。在这里，我们讨论肠道耶尔森氏菌(YE)的毒力因子是否和如何影响这种相互关系，以及是否和如何使用微生物区系的特定成分来干扰YE的致病性。为此，我们将使用Ye野生型和等基因突变株，一个实验性的小鼠耶尔森氏菌感染模型，包括无菌(GF)和生态组小鼠，以及元基因组分析来解决特定的假设。这些研究结果将为YE、肠道微生物区系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.