头花蓼内生菌抗尿路感染耐药菌化学小分子的发现及其作用机制研究

头花蓼是贵州特色苗药，对尿路感染及其耐药菌疗效突出。由于抗生素的滥用导致尿路感染产生耐药菌，使常用抗生素的临床疗效普遍降低。内生菌与宿主的代谢产物有着密切联系，从头花蓼内生菌的代谢产物中发现抗（或协同抗生素抗）耐药菌的活性化合物，对治疗耐药菌引起的尿路感染具有重要意义。前期研究已发现2株头花蓼内生菌的代谢产物具有抗尿路感染耐药菌活性，且这些内生菌与头花蓼既有结构相同或相关的代谢产物，内生菌与头花蓼以及内生菌之间也存在明显不同的代谢物质。本项目拟通过广泛采集贵州不同生长条件下头花蓼的内生菌，以尿路感染耐药菌为指示菌，筛选出更多的活性内生菌株；通过UHPLC-DAD-Q/TOF-HRESIMS/MS分析和现代分离、鉴定手段，从其代谢物中获得具有抗尿路感染耐药菌活性的新型化合物；利用RT-PCR及SDS-PAGE等分子生物学技术探索活性化合物的作用机制。

Polygonum capitatum is an ethnic Miao's characteristic herb in Guizhou province with proven therapeutic effect against urinary tract infection and its drug-resistant bacteria. Due to the generation of drug-resistant bacteria from abuse of antibiotics, the clinical curative effect of urinary tract infection often declined. The close relationship between metabolites of endophytes and their hosts suggested that it is of particular importance to search for new and active compounds from endophytes of P. capitatum for the treatment of resistant urinary tract infections. Previous efforts has resulted in the discovery of two strains of endophytes of P. capitatum whose metabolites showed good inhibitory activity against the resistant bacteria of urinary tract infection. Chemical analysis indicated that the two endophytes and P. capitatum itself shared some same metabolites, but differences were also found between the two endophytes as well as the endophytes and P. capitatum. In this project, collection of a wider range of endophytes from different aeres of P. capitatum will be carried out for the screening of more active endophytes against resistant strains of urinary tract infection. The metabolites of the active endophytes will then been analyzed by UHPLC-DAD-Q/TOF-HRESIMS/MS, and the compounds with unreported structures will be deemed the target molecules for isolation and structural elucidation. The anti- resistance mechanisms of the active compounds will be investigated by using methods of molecular biology such as RT-PCR and polyacrylamide gel electrophoresis.