Carnosol attenuates <i>Acinetobacter baumannii</i> virulence by interfering with indole-mediated quorum sensing

Many bacterial pathogens utilize quorum sensing (QS) signals to modulate the biological functions in a cell density-dependent manner. <i>Acinetobacter baumannii</i> is a harmful pathogen and a major cause of hospital-acquired infections due to its severe drug-resistance and pathogenic nature. Therefore, the development of innovative antibacterial strategies for <i>A. baumannii</i> infections is important. Earlier studies have proved that <i>A. baumannii</i> utilizes N-acyl-L-homoserine lactones (AHLs) and indole signalling systems to modulate its biological functions and virulence. Here, we report that carnosol, which is isolated from <i>Salvia officinalis</i> L. (<i>S. officinalis</i>), inhibited the pathogenicity of <i>A. baumannii</i> by interfering with indole-mediated quorum sensing. Phenotypic and virulence experiments have revealed that carnosol decreased the formation of biofilms, motility, and cytotoxicity of <i>A. baumannii</i>, without affecting its growth rate. Genetic and biochemical analysis results showed that carnosol reduced the regulatory effect of AbiR on the transcription of target genes by inhibiting the binding of AbiR to the promoters of these genes. Our results suggest that the indole QS system of <i>A. baumannii</i> could be used as a new target and that carnosol might be developed as a new anti-virulence agent against <i>A. baumannii</i> infections.诸多细菌致病菌可借助群体感应（quorum sensing，QS）信号，以细胞密度依赖的方式调控自身生物学功能。鲍曼不动杆菌（Acinetobacter baumannii）是一种高致病性致病菌，因其极强的耐药性与致病特性，已成为医院获得性感染的主要诱因之一。因此，针对鲍曼不动杆菌感染开发新型抗菌策略具有重要意义。既往研究已证实，鲍曼不动杆菌可通过N-酰基-L-高丝氨酸内酯（N-acyl-L-homoserine lactones，AHLs）与吲哚信号系统调控自身生物学功能与毒力。本研究发现，从药用鼠尾草（Salvia officinalis L.，简称S. officinalis）中分离得到的鼠尾草酸可通过干扰吲哚介导的群体感应，抑制鲍曼不动杆菌的致病性。表型与毒力实验结果显示，鼠尾草酸可降低鲍曼不动杆菌的生物被膜形成能力、运动能力与细胞毒性，且对其生长速率无显著影响。遗传与生化分析结果表明，鼠尾草酸可通过抑制AbiR与靶基因启动子的结合，削弱AbiR对靶基因转录的调控作用。本研究结果提示，鲍曼不动杆菌的吲哚QS系统可作为新型抗菌靶点，而鼠尾草酸有望被开发为针对鲍曼不动杆菌感染的新型抗毒力制剂。