铜绿假单胞菌耐药进化中的群体感应及阻控

微生物耐药是当前全球最严峻的公共健康问题之一。虽然环境耐药近来得到了广泛关注，但其内在机制仍有待深入。本项目拟以环境中广泛存在的铜绿假单胞菌为模式菌株，以微生物细胞间“对话”即群体感应为切入，进行环境微生物耐药的形成机制及阻控研究。通过设定抗生素、非抗生素等典型微污染条件，对比群体感应信号分泌、受体活性、调节产物等差异，阐明群体感应对典型环境微污染的响应规律；通过模拟进化试验，分析群体感应对氧化损伤、DNA损伤的影响及调控，解析环境微生物耐药进化的群体感应机理；通过群体感应淬灭及非淬灭对比，分析群体感应对耐药菌生物膜形成、抗性基因水平转移的影响及调控，探究环境微生物耐药传播的群体感应机制；通过iDynoMiCS和Balaban模型建立，提出环境耐药阻控的群体感应策略。项目实施不仅有助于深入理解环境微生物耐药形成和传播，而且可为耐药阻控提供前瞻性科学依据，具有重要的科学意义和潜在的应用价值。

Microbial antibiotic resistance is one of the most serious public health issues in the world. Although the antibiotic resistance in the environment has received worldwide attentions recently, its fundamental mechanisms still need to be deeply explored. This project will employ Pseudomonas aeruginosa, the universal bacteria in various conditions, as the model strains and take bacterial "dialogue", i.e. quorum sensing, as cutting point, to study the formation mechanism and blocking strategy of microbial antibiotic resistance in the environment. First, the differences of signal secretion, receptor activities and product contents under sub-lethal antibiotics and other pollutants exposures will be compared, with aim to clarify the response law of quorum sensing to typical pollutants in the environment. Second, the influence and regulation of quorum sensing on oxidative damage and DNA damage under simulated evolutionary conditions will be analyzed, with aim to elucidate the quorum sensing mechanism on the evolution of microbial antibiotic resistance in the environment. Third, the influence and regulation of quorum sensing on biofilm formation and horizontal transfer of antibiotic resistance genes under quorum and quorum quenching conditions will be compared, with aim to explore the quorum sensing mechanism on the transmission of microbial antibiotic resistance in the environment. Last but not the least, the iDynoMiCS and Balaban models will be constructed, with aim to propose the strategy for antibiotic resistance blocking based on the theory of quorum sensing. The implementation of this project is not only conducive to understand the formation and transmission of microbial antibiotic resistance in the environment, but can provide forward-looking scientific basis for antibiotic resistance control, which has important scientific significance and potential application value.