霍乱弧菌溶血素（HlyA）介导的病理损伤是霍乱病理生理学的重要研究内容。迄今为止，HlyA的调节机制尚不清楚。课题组基于前期有关叉头结合蛋白(Fha)的研究基础，提出了“霍乱弧菌VI型分泌系统FHA蛋白可通过调控PrtV蛋白酶的表达而影响HlyA溶血活性”的工作假说。本项目的主要研究涉及：①以非O1/非O139群霍乱弧菌fha基因敲除菌株和回复菌株为模型菌，观察fha基因对HlyA活性的影响；②通过RNA-Seq技术分析fha基因敲除前后转录组改变，筛选Fha蛋白调控HlyA活性的差异基因；③以△fha△hlyA、△fha△prtV基因双敲菌及基因回复菌为模型菌，观察Fha蛋白对金属蛋白酶PrtV表达的影响，以及Fha蛋白通过PrtV产生HlyA降解效应及HlyA介导的病理损伤变化。预期研究结果对丰富霍乱分子发病学理论有重要意义，对寻求相关的干预方法具有潜在价值。

The pathological injury induced by Vibrio cholerae hemolysin (HlyA) is an important research content in the pathophysiology of cholera. To date, the regulatory mechanism of HlyA is not yet clear. Based on the previous research foundation of forkhead binding protein (Fha), we proposed the working hypothesis that "the FHA protein of the V. cholerae type VI secretion system affects the hemolytic activity of HlyA by regulating the expression of PrtV proteinase." The main research of this project involves：（1）The non-O1/non-O139 Vibrio cholerae fha knockout strains and revertants were used as model bacteria to observe the effects of fha gene on HlyA activity；（2）Analysis of transcriptome changes before and after fha gene knockout by RNA-Seq technology and screening for differential genes that regulate the activity of HlyA by Fha protein；（3）The △fhaΔhlyA and △fha△prtV double knockout and gene recovery strains were used as model bacteria to observe the effect of Fha protein on the expression of metalloproteinase PrtV, and the degradation effect of Fha protein through PrtV on HlyA degradation and pathological changes mediated by HlyA. It is expected that the results of the study will be of great significance for enriching the molecular pathogenesis of cholera and have potential value in seeking relevant intervention methods.