5个恶唑烷酮类新化合物对铜绿假单胞菌群体感应系统的抑制研究  

Study on inhibition of quorum sensing system of Pseudomonas aeruginosa by five novel oxazolidinones

作　　者：汤倩玲 温福龙 袁阳 吴怡 马文博 褚以文[1] 赵克雷 Tang Qianing;Wen Fuong;Yuan Yang;Wu Yi;Ma Wenbo;Chu Yiwen;Zhao Keei(Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province,Sichuan Industrial Institute of Antibiotics,School of Pharmacy,Chengdu University,Chengdu 610106)

机构地区：[1]抗生素研究与再评价四川省重点实验室,四川抗菌素工业研究所,药学院,成都大学,成都610106

出　　处：《中国抗生素杂志》2023年第10期1135-1140,共6页Chinese Journal of Antibiotics

基　　金：四川省科技厅杰出青年科技基金项目(No.2021JDJQ0042);成都大学高层次人才培育项目(No.2081920066)。

摘　　要：目的 以铜绿假单胞菌PAO1为模式菌,研究恶唑烷酮类新化合物对铜绿假单胞菌群体感应系统的抑制作用及其作用机制。方法 测定5个恶唑烷酮类新化合物对PAO1生物膜、绿脓菌素、运动能力抑制活性,采用qRT-PCR测试其对群体感应相关基因的下调作用,并评估化合物对秀丽隐杆线虫感染模型的保护活性。结果 化合物SIIA-MA2与SIIA-MA4对PAO1生物膜、绿脓菌素、运动能力具有较强的抑制活性,其作用机制均是并显著下调PAO1中10个已知的受群体感应系统正调控的基因。化合物SIIA-MA2与SIIA-MA4对秀丽隐杆线虫感染模型具有良好的体内保护活性,其中化合物SIIA-MA2对急性感染模型具有显著保护活性;化合物SIIA-MA4对慢性感染模型具有显著保护活性。结论 恶唑烷酮类新化合物SIIA-MA2和SIIA-MA4通过抑制PAO1群体感应系统发挥抗感染作用。Objective To evaluate the inhibitory activities of novel oxazolidinone compounds on the quorum sensing(QS)system of P.aeruginosa reference strain PAO1.Methods The influences of five novel oxazolidinones on the QS system,biofilm formation,pyocyanin formation,and motility ability of P.aeruginosa PAO1 were tested,followed by checking the expression of 10 typical genes that are positively regulated by the QS system of P.aeruginosa using qRT-PCR.Caenorhabditis elegans-P.aeruginosa PAO1 infection model was employed to explore the in vivo protective effect of compounds SIIA-MA2 and SIIA-MA4.Results Compounds SIIA-MA2 and SIIA-MA4 significantly inhibited the production of biofilm,pyocyanin,and bacterial motility of P.aeruginosa PAO1,and the expression levels of QS-controlled genes were significantly down-regulated.Furthermore,the treatment of compound SIIA-MA2 significantly protected C.elegans from the fast-killing of P.aeruginosa PAO1,while the compound SIIA-MA4 mainly functioned in the slow-killing assay.Conclusion This study reveals anti-QS activities of the new oxazolidinone compounds SIIA-MA2 and SIIA-MA4 against P.aeruginosa,and provides a method for the discovery of novel anti-infectious drugs.

关 键 词：恶唑烷酮类化合物 铜绿假单胞菌 群体感应 群体感应抑制剂 

分 类 号：R978.1[医药卫生—药品]