咖啡酸对铜绿假单胞菌群体感应抑制探究  

The inhibitory effect of caffeic acid on Pseudomonas aeruginosa QS system and its target

作　　者：宋文旭 冯玉琦 韩啸枫 王世伟 徐翠香[2] 张海祥[2] 沈立新[1] SONG Wenxu;FENG Yuqi;HAN Xiaofeng;WANG Shiwei;XU Cuixiang;ZHANG Haixiang;SHEN Lixin(College of Life Sciences,Northwest University,Xi’an 710069,China;Shaanxi Provincial Key Laboratory of Infection and Immune Diseases,Shaanxi ProvincialPeople’s Hospital,Xi’an 710068,China)

机构地区：[1]西北大学生命科学学院,陕西西安710069 [2]陕西省人民医院陕西省感染与免疫疾病重点实验室,陕西西安710068

出　　处：《西北大学学报（自然科学版）》2024年第5期867-875,共9页Journal of Northwest University（Natural Science Edition）

基　　金：陕西省自然科学基金(2018ZDXM-SF-004);陕西化生基础科学研究项目(22JHZ008);陕西省感染与免疫疾病重点实验室开放基金(2023-KFZD-3)。

摘　　要：世界范围内,病原菌对抗生素的耐药性日趋严峻,但药物研发效率日趋缓慢,迫切需要新的抗感染药物或药物作用靶点。铜绿假单胞菌群体感应系统(quorum sensing,QS)与其致病性密切相关,寻找靶向QS系统的抑制剂是新型抗感染药物新策略。前期研究发现,以咖啡酸为主要成分的大血藤提取物对铜绿假单胞菌的群体感应具有转录抑制作用。进一步探究了咖啡酸对铜绿假单胞菌的QS系统相关基因的表达和毒性因子产生的抑制作用;通过分子对接结合缺失突变体感染白菜模型检测,探究了咖啡酸的作用靶点。结果表明:咖啡酸显著抑制铜绿假单胞菌QS系统相关基因rhlR、rhlI、pqsA、pqsR及其调控的毒性因子的编码基因如phzA 1、lasB等,进一步抑制该类毒性因子的产生和降低了细菌的运动性和生物被膜,最终降低了铜绿假单胞菌的感染性,其可能通过靶向pqs系统发挥其QS抑制作用。Antimicrobial resistance(AMR)of bacteria has increased worldwide dramatically and the development of new antibiotics has been slowed down.Therefore,it is urgent to explore new anti-infective drugs or therapeutics.Quorum sensing(QS)system of pathogen is closely related to its pathogenicity.QS system inhibitors could significantly reduce the pathogenicity of pathogen.QS system is mainly composed of las,rhl,and pqs systems and Sargentodoxae Caulis extracts mainly containing caffeic acid which has shown QSI activity.In this study,we proved the antivirulence and antipathogenicity of caffeic acid against Pseudomonas aeruginosa at the transcript and product level,then we further investigate the target of caffeic acid in QS system by using molecular docking combining the mutant strains determination.The results indicated that caffeic acid could reduce the expression of QS-related genes rhlR,rhlI,pqsA,pqsR as well as virulence related genes such as phzA 1、lasB.Motility ability and biofilm were also suppressed obviously by caffeic acid.Chinese cabbage and fruit fly infection model analysis verified the antipathogenicity of caffeic acid.Caffeic acid might inhibit QS system by targeting the pqs system based on the docking analysis and gene mutant strains evaluation on caffeic acid.

关 键 词：咖啡酸 铜绿假单胞菌 群体感应系统 毒力因子靶点 PQS 

分 类 号：R378[医药卫生—病原生物学]