副溶血性弧菌（Vibrio parahaemolytics，VP）是广泛存在于水产品中的致病菌。目前已证实溶血素（TDH/TRH）是VP主要致病因子。我国水产品源VP中tdh/trh携带率很低，但引起的食品中毒事件常有发生，而许多临床株不携带溶血基因。说明此类VP具有潜在的致病能力，但其危害形成机制仍未有阐明。本项目拟在利用MLST分析不携带溶血基因的水产品源VP和临床株的基础上，选择代表性菌株进行细胞和动物水平的毒力分析获得毒力差异菌株。进而进行比较基因组学、转录组学和蛋白组学分析，挖掘潜在致病因子。同时分析宿主受侵染前后的差异表达基因/蛋白，挖掘潜在受体蛋白。采用酵母双杂交技术验证VP致病因子与宿主受体的相互作用关系。通过靶点基因的敲除及回复分析，阐明相关基因功能。本项目旨在揭示不携带溶血基因的VP的危害形成，拓展VP的危害形成机制新认知，为评估食品源VP致病性和控制危害提供理论基础。

Vibrio parahaemolyticus is the leading cause of foodborne outbreaks, particularly associated with aquatic products. The virulence factors of V. parahaemolyticus are mainly attributed to TDH and TRH. However, few isolates from aquatic products in our nation possess tdh/trh genes although they often cause food poisoning, indicating their high disease risk. So far, the overall mechanism of V. parahaemolyticus pathogenesis without tdh/trh genes remains unclear. Via MLST analysis on V. parahaemolyticus in aquatic products and clinical isolates from China, pathology study will be performed on selective V. parahaemolyticus strains and higher virulent strains will be isolated. Putative virulence factors of these strains will be identified by comparative genomics, transcriptomics, and proteomics studies. Besides, the differences on gene and protein expression within the host cells will also be investigated and potential receptors of different virulence factors will be identified. The protein-protein interaction between virulence factors and host receptors will be confirmed by yeast two-hybrid experiment. Through knock out of different target genes and related complementary experiments, function of different genes will be elucidated. Finally, we will illustrate the pathogenic mechanism of V. parahaemolyticus without tdh/trh genes, which will provide a theoretical basis for identification, preventing and controlling the V. parahaemolyticus during the production process of aquatic products.