Signal transduction mechanism of Ps. aeruginosa biofilm dispersion response

描述（由申请人提供）：我们实验室最近的研究已经证明，铜绿假单胞菌产生一种小信使分子，其诱导生物膜细胞簇的解聚，并导致从生物膜转换为无菌生活方式。初步结果表明，与未被诱导分散的生物膜细菌相比，这些分散的细菌对抗生素治疗明显更敏感。我们希望表征顺式-2-癸烯酸介导的生物膜分散反应中的信号转导机制。在执行这项工作中，我们建议确定系统的组成部分，负责在生物膜分散反应的信号转导，并确定这些基因，由这个信号系统调节。在进行这项工作时，我们将使用分子方法来表征传感器，反应调节器和靶DNA的相互作用，并分析蛋白质-蛋白质相互作用和DNA相互作用的存在和不存在的信号。 公共卫生相关性：本申请提出了将产生重要信息的工作，这些信息导致理解铜绿假单胞菌中生物膜分散响应的机制。这项研究的结果有望为细菌生物膜感染的治疗带来新的和改进的策略。人工诱导生物膜中分散的潜力包括生物膜感染的增强治疗、烧伤的改善治疗、生物膜从表面的改善去除以及临床、家庭和工业环境中疾病预防的新机制。

DESCRIPTION (provided by applicant): Recent studies in our laboratory have demonstrated that P. aeruginosa produces a small messenger molecule that induces the disaggregation of biofilm cell clusters and results in a switch from a biofilm to a planktonic lifestyle. Preliminary results have demonstrated that these dispersed bacteria are significantly more susceptible to antibiotic treatment when compared to biofilm bacteria that have not been induced to disperse. We wish to characterize the mechanism of signal transduction in the biofilm dispersion response mediated by cis-2-decenoic acid. In performing this work we propose to identify the components of the system that are responsible for signal transduction in the biofilm dispersion response and to identify those genes that are regulated by this signaling system. In performing this work we will use molecular approaches to characterize the interactions of the sensors, response regulators and target DNA, and analyze protein-protein interactions and DNA interactions in the presence and absence of signal. PUBLIC HEALTH RELEVANCE: The current application proposes work that will yield important information leading to an understanding of the mechanism of the biofilm dispersion response in P. aeruginosa. Findings from the proposed research are expected to lead to novel and improved strategies for the treatment of bacterial biofilm infections. The potential for artificial induction of dispersion in biofilms includes enhanced treatment of biofilm infections, improved treatment of burns, improved removal of biofilm from surfaces, and novel mechanisms for disease prevention in clinical, household and industrial settings.