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表明，铜绿假单胞菌产生一种小信使分子，诱导生物膜细胞簇的分解，并导致从生物膜到浮游生活方式的转变。初步结果表明，与未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-2-十烯酸介导的生物膜分散反应中的信号转导机制。在进行这项工作时，我们建议确定在生物膜分散反应中负责信号转导的系统的组成部分，并确定受该信号系统调节的基因。在进行这项工作时，我们将使用分子方法来表征传感器、反应调节因子和靶DNA的相互作用，并分析在存在和不存在信号的情况下蛋白质-蛋白质相互作用和DNA相互作用。

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.