The molecular mechanisms of bacterial outer membrane vesicle formation

细菌外膜囊泡形成的分子机制

• 批准号: 7883454
• 负责人: Marvin Whiteley
• 金额: $ 35.74万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-15 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7883454
• 关键词: Bacteria; Bacterial Toxins; Binding; Biochemical; Bulla; Cells; Charge; Communication; Development; Disease; Divalent Cations; Eukaryotic Cell; Figs - dietary; Genetic; Goals; Gram-Negative Bacteria; Growth; Individual; Infection; Laboratories; Lipopolysaccharides; Mediating; Membrane; Membrane Proteins; Methodology; Modeling; Molecular; Molecular Models; Nature; Pathogenesis; Pathogenicity; Peptidoglycan; Periplasmic Proteins; Physiological; Population; Production; Proteins; Pseudomonas aeruginosa; Research Personnel; Role; Signal Transduction; Signaling Molecule; Sodium Chloride; Techniques; Testing; Toxin; Vesicle; Virulence; Virulence Factors; antimicrobial; base; chelation; chemical genetics; extracellular; insight; intercellular communication; molecular modeling; novel; pathogen; programs; research study; technology development; trafficking

DESCRIPTION (provided by applicant): A large number of Gram-negative bacteria naturally produce extracellular membrane vesicles (MVs). These vesicles are derived from the outer membrane (OM) and contain OM and periplasmic proteins. MVs are an important component of bacterial virulence as they serve as trafficking vehicles for bacterial toxins to eukaryotic cells. In addition to trafficking toxins, our laboratory recently discovered that the opportunistic pathogen Pseudomonas aeruginosa utilizes MVs to traffic the cell-cell signaling molecule PQS between P. aeruginosa cells. Since PQS signaling is required for virulence, MVs are a critical component of P. aeruginosa pathogenicity. Although the roles of MVs in pathogenesis are clear, the molecular mechanism of MV formation is not currently understood. The goal of this proposal is to determine the molecular mechanism of MV formation in P. aeruginosa. To this end, a molecular model for MV formation has been developed, and three specific aims are proposed to test this model. These specific aims propose genetic, biochemical, and physiological techniques to exact a role for PQS (specific aim 1), lipopolysaccharide (specific aim 2), and pg-associated OM proteins (specific aim 3) in MV formation, with the ultimate goal of precisely defining the mechanism of MV formation. Due to their role in toxin and signal trafficking, understanding how MVs are produced will provide new insight into P. aeruginosa signaling and disease. Ultimately, understanding the molecular mechanism of MV formation may provide a novel target for antimicrobial development through development of technology to control MV production. Bacterial communication within a population is critical for pathogenicity of many bacteria, including the bacterium Pseudomonas aeruginosa. The goal of this project is to provide a fundamental understanding of how P. aeruginosa communicates, with the ultimate goal of devising ways to disrupt this communication.

描述（由申请人提供）：大量革兰氏阴性细菌自然产生细胞外膜囊泡（MVS）。这些囊泡源自外膜（OM），并包含OM和周质蛋白。 MV是细菌毒力的重要组成部分，因为它们是用于真核细胞的细菌毒素的运输车辆。除了运输毒素外，我们的实验室最近发现，铜绿假单胞菌的机会性病原体利用MVS来访问铜绿假单胞菌细胞之间的细胞细胞信号分子PQ。由于毒力需要PQS信号传导，因此MV是铜绿假单胞菌致病性的关键组成部分。尽管MV在发病机理中的作用很明显，但目前尚不了解MV形成的分子机制。该建议的目的是确定铜绿假单胞菌中MV形成的分子机制。为此，已经开发了用于MV形成的分子模型，并提出了三个特定目的来测试该模型。这些特定目的提出了遗传，生化和生理技术，以确切起作用PQ（特定目标1），脂多糖（特定目标2）和PG相关的OM蛋白（特定的目标3）（在MV形成中），并具有精确定义MV形成机制的最终目标。由于它们在毒素和信号运输中的作用，了解如何生产MV将为铜绿假单胞菌信号传导和疾病提供新的见解。最终，了解MV形成的分子机制可能通过技术来控制MV生产来为抗菌发育提供一个新的目标。人群中的细菌交流对于包括铜绿假单胞菌在内的许多细菌的致病性至关重要。该项目的目的是提供对铜绿假单胞菌如何交流的基本理解，其最终目标是设计方法来破坏这种交流。