谷胱甘肽阻抑支气管扩张铜绿假单胞菌感染的群体感应机制研究

支气管扩张（支扩）是三大慢性气道炎症疾病之一，铜绿假单胞菌（PA）慢性感染多见，是支扩病情进展重要原因。因PA耐药严重，难以根治，目前亟待新的抗菌防治策略。群体感应（QS）参与调控PA毒力、生物膜、耐药等多种表型，在PA感染中发挥重要作用。既往发现氧化应激可影响QS，但具体机制不详。谷胱甘肽(GSH)是重要抗氧化剂，影响PA多种表型，但机制未完全阐明。MexT是一种氧化应激感受器，与QS存在紧密联系。本研究发现GSH的合成基因gshA点突变后能显著激活QS系统，促进PA生长速率以及毒力分子、生物膜形成。在此，我们提出假说：gshA点突变可调控氧化还原水平，通过MexT间接调控QS系统，进而影响PA致病性和耐药性。本研究拟通过体外和动物实验深入研究GSH影响QS的分子机制及在PA慢性肺部感染中的作用，为支扩PA慢性感染的治疗提供新的思路和手段。

Bronchiectasis is one of the three major chronic airway inflammatory diseases. Chronic infection of Pseudomonas aeruginosa (PA) is common in bronchiectasis, which is an important reason for the progress of bronchiectasis. Due to the serious antimicrobial resistance of PA, it is difficult to cure it. At present, new antibacterial prevention and treatment strategies are urgently needed. Quorum sensing (QS) is involved in the regulation of PA virulence, biofilm, antimicrobial resistance and other phenotypes, and plays an important role in PA infection. It has been found that oxidative stress can affect QS, but the specific mechanism is unknown. Glutathione (GSH) is an important antioxidant, which affects many phenotypes of PA, but the mechanism is also unknown. MexT serves as an oxidative stress sensor, which is closely related to QS. Our study found that the point mutation of GSH synthesis gene-gshA can significantly activate QS system and promote the growth rate, the formation of virulence molecules and biofilm of PA. Here, we propose a hypothesis: gshA point mutation can interfere with the redox level, indirectly regulate the QS system through MexT, and then affect the pathogenicity and antimicrobial resistance of PA. This study intends to deeply study the molecular mechanism of GSH affecting QS and its role in PA chronic lung infection through in vitro and animal experiments, so as to provide new ideas and methods for the treatment of PA chronic infection in Bronchiectasis.