Enterococcus faecium H1激发霍乱弧菌在肠道环境条件下VPI-1/TCP毒力岛水平转移的分子机制

霍乱弧菌曾造成7次世界性霍乱流行，至今仍肆虐人间。霍乱弧菌基因组上有许多来源于其他微生物的大片段基因簇，编码与体内定殖及发病症状相关的基因，称为“毒力岛”。霍乱弧菌毒力岛的基因水平转移导致霍乱弧菌毒力进化上的“量子跃迁”，是霍乱病在地球上周期性爆发的关键原因。霍乱弧菌在动物宿主体内定殖依赖TCP纤毛的存在，tcp基因簇分布在VPI-1/TCP毒力岛上，但该毒力岛如何转移一直是霍乱弧菌领域的未解之谜，制约着对霍乱弧菌分子进化的认识和对霍乱病的控制。我们在前期研究中发现，霍乱弧菌VPI-1/TCP毒力岛的水平转移需要满足两个条件：供体菌和受体菌必须共存；选择压力必须有利于供体菌的生存。我们发现肠道微生物能够帮助霍乱弧菌VPI-1/TCP毒力岛在幼鼠肠道内实现水平转移。在此基础上，我们将进一步研究霍乱弧菌VPI-1/TCP的生化本质和水平转移的调控机制，为最终阐明霍乱弧菌的毒力进化机制奠定基础。

Vibrio cholerae is a human pathogen which colonizes small intestines of host, resulting in the onset of a severe diarrheal disease known as cholera. In order for V. cholerae to successfully colonize the host, it must express a series of virulence factors, including toxin-coregulated pilus (TCP). The genes involves in the biosynthesis of TCP reside in a pathogenicity island, called “VPI-1/TCP island”. However, how V. cholerae aquire and transfer this island is not known. In our preliminary studies, using an infant mouse model, we discovered that the.horizontal transfer of VPI-1/TCP island occurs in host small intestines and requires a member of gut microbiota, identified as Enterococcus faecium. Based on these results,we hypothesize that signals from mammalian hosts and gut microbiota initiate VPI-1/TCP horizontal transfers and provide TCP- V. cholerae selective advantages once aquired TCP. In this application, we will use genomics, genetics, and biochemical approaches to further study the molecular mechanisms of VPI-1/TCP island horizontal transfer. Our studies will shed lights on evolutionary bases of emerging and re-emerging of infectious agents.