霍乱弧菌非产毒株prophage编码T6SS依赖的新效应子靶向特异杀伤产毒株机制研究

微生物资源的开发和利用在自然资源高效利用和可持续发展等方面起着重要的作用。霍乱弧菌由产毒和非产毒两种菌株构成，且产毒株的致病感染性依旧是当今社会重要的公共卫生问题。本项目我们率先报道环境分离的非产毒株1928通过T6SS（Type VI Secretion System）高效杀伤大流行产毒株C6706、N16961和V52现象。进一步研究发现非产毒株三个已知效应子点突变失活或敲除后依旧能够通过T6SS杀伤产毒株但不再杀伤大肠杆菌、嗜水气单胞菌和产气肠杆菌，因此，我们大胆推测菌株1928存在以T6SS依赖的方式分泌新的效应子，可以高效且特异杀伤产毒株。定量蛋白质组学和进一步实验结果首次证实前噬菌体携带的潜在新效应子对产毒株特异杀伤。综上所述，前噬菌体编码新的效应子探索对全面深入理解T6SS杀菌机制以及对利用非产毒株微生物资源开发靶向治疗霍乱与疫情防控具有重要科学意义。

The development and utilization of microbial resources play an important role in the efficient utilization and sustainable development of natural resources. Vibrio cholerae is composed of toxigenic and non-toxigenic strains. The infection of pathogenic bacteria has become an important public health problem in today's society. In this investigation, we firstly reported a phenomenon that a non-toxigenic strain 1928 isolated from the environment effectively kills pandemic strains C6706, N16961 and V52. Further study found that all known effectors inactivation by point mutation and knockout methods are still effective in killing the Vibrio cholerae pandemic strains but not in Escherichia coli MG1655, Aeromonas hydrophila and Enterobacter aerogenes. Therefore, We boldly speculated that the non-toxin-producing strain 1928 secrets new unknown effector that are highly effective and specific to kill pathogenic Vibrio cholerae strains in a T6SS dependent fashion.The results of quantitative proteomics and further experiments showed that the gene carried by the prophage did specifically kill toxigenic strains. In summary, the exploration of novel effector has important scientific significance for the comprehensive understanding of T6SS-mediated killing mechanism and the development of microbial resources for targeted treatment and prevention of cholera.