锌胁迫抑制铜绿假单胞菌群体感应系统的作用机制研究

铜绿假单胞菌是造成医院获得性感染最主要的病原菌之一并且具有极强的抗生素耐药性，其中该菌的群体感应系统对其致病性和耐药性均起到了至关重要的调控作用。因此，以群体感应为靶标开发新型治疗手段是临床抗感染与抗耐药的一项重要策略。金属锌离子作为一种传统的抗菌物质，研究发现它能有效抑制铜绿假单胞菌群体感应系统的活性，但其中的作用机理尚未明确。本项目将在分子水平深入探讨锌胁迫对群体感应中两大重要信号系统（Las和Iqs）的作用机制，借助基因组筛选和转录组测序的高通量技术全面系统地解析锌胁迫与调节锌稳态最重要的双组份系统CzcS-CzcR对铜绿假单胞菌群体感应系统和其他重要生理过程的调控网络。研究结果将进一步完善对群体感应逆境响应的认知，并为锌离子药物的临床抗感染与抗耐药应用提供理论依据和新的方案。

Pseudomonas aeruginosa is a major cause of nosocomial infections which is equipped with extensive antibiotic resistance. Its virulence and antibiotic resistance are mainly controlled by its Quorum Sensing (QS) system. Thus, inactivating QS system is regarded as a promising strategy for the treatment of infections caused by P. aeruginosa. As an ancient antimicrobial compound, zinc was reported to be capable of inhibiting QS activity in P. aeruginosa, but the underlying regulatory mechanisms remain elusive. In this proposal, we aim to investigate how zinc stress inhibits the two important QS signaling systems (Las and Iqs) at molecular level. By employing the high-throughput techniques such as whole genome screening and transcriptome sequencing, we expect to comprehensively understand the regulatory network between zinc stress including its responsive two-component system CzcS-CzcR and QS. Findings in this study will not only expand our understanding on the diverse QS behaviors in response to different environmental conditions but also provide insights and strategies for the clinical use of zinc-based anti-infective drugs.