群体感应系统调控pks+禽致病性大肠杆菌基因毒素机制探讨

基因毒素（Colibactin）作为一种新发现的大肠杆菌毒素，具有破坏真核细胞DNA双链的毒性，由pks毒力岛编码，在肠道大肠杆菌中发挥致结直肠癌等重要作用。.然而，基因毒素在肠道外大肠杆菌、尤其是禽致病性大肠杆菌(APEC)中的调控与毒力作用机制鲜见报道。.本课题组前期发现细菌密度感应系统群体感应（QS）深入调控APEC毒力。在此基础上，发现培养基中添加QS信号（C6HSL与AI-2）可激活基因毒素多个重要合成基因的表达，影响菌株细胞毒性与致巨红细胞症能力。然而，QS系统是否通过调节基因毒素合成而影响细菌细胞毒性、及其调控机制，均期待深入研究。.本项目首先明确QS系统影响APEC菌株基因毒素表达的现象，随后分析QS是否通过clbR与S-腺苷甲硫氨酸途径影响基因毒素合成，旨在深入探讨QS调控下基因毒素活性变化在APEC感染致病进程中的作用及引起细胞基因损伤分子机制。

As a newly discovered E. coli toxin, the colibactin has the toxicity of destroying the DNA double strand of eukaryotic cells, is encoded by the pks virulence island, and plays important roles like induce colorectal cancer in the enteropathogenic E. coli..However, the regulation and virulence mechanisms of colibactin in extraintestinal pathogenic Escherichia coli (ExPEC), especially avian pathogenic Escherichia coli (APEC), have rarely been reported..Our group found that the bacterial density sensing system quorum sensing (QS) in-depth regulate APEC virulence. On this basis, it was found that the addition of QS signaling molecule (C6HSL and AI-2) in the medium can activate the expression of several important synthetic genes of colibactin, affecting the cytotoxicity of the strain and the ability to cause erythroblastosis. However, whether the QS system affects bacterial cytotoxicity and its regulatory mechanisms is expected to be further studied..This project will firstly clarify the phenomenon that QS system affects the expression of cytotoxicity in APEC strain, and then analyzed whether QS affects the synthesis of cytotoxicity through clbR and S-adenosylmethionine pathway, and finally explored the change of cytotoxicity activity, the role of pathogenic process, and the molecular mechanism of cell damage under QS regulation in APEC infection.