IasB is Essential for Surface Motility in P. aeruginosa

IasB 对于铜绿假单胞菌的表面运动至关重要

• 批准号: 6806713
• 负责人: JAYNE B ROBINSON
• 金额: $ 22.13万
• 依托单位: UNIVERSITY OF DAYTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6806713
• 关键词: Pseudomonas aeruginosa; bacterial genetics; bacterial proteins; biofilm; biological signal transduction; butyrolactone; cell component structure /function; cilium /flagellum motility; elastases; enzyme mechanism; flagellum; gene expression; gene mutation; metalloendopeptidases; microarray technology; microbiology; pilus; proteomics; quorum sensing; virulence

DESCRIPTION (provided by applicant): Pseudomonas aeruginosa is a ubiquitous and important opportunistic pathogen that possesses an impressive arsenal of virulence factors. Elastase, a metalloprotease encoded by the lasB gene, contributes to virulence by degrading or inactivating tissue and immune system components. The expression of lasB requires both the las quorum-sensing (QS) system and PQS. Little is known about the role elastase plays in the life of this bacterium. Evidence that lasB mutant cells are severely deficient in both twitching and swarming motility was recently discovered in our lab and is presented here for the first time. Surface associated motility is essential for survival and dispersal of bacterial populations and plays a defining role in biofilm formation. The proposed research will investigate the mechanism(s) by which elastase affects these two forms of motility. Twitching motility is dependent upon PilT mediated retraction of the Type IV pilus. Pilus retraction is inhibited in lasB mutant cells, thus our studies will focus on the mechanism by which LasB affects pilus retraction. Swarming motility requires both flagella and rhamnolipids. The number and position of flagella are altered on lasB mutant cells. Additionally, lesser amounts of C4-homoserine lactone (HSL) are produced by lasB mutant cells. The production of rhamnolipids, pyocyanin, and pyoverdin are all controlled by the rhl quorum-sensing system for which C4-HSL is the cognate signal. The lasB gene itself is regulated by QS and the proposed research seeks to determine how elastase affects AHL production in P. aeruginosa. The pleiotropic effects of the lasB mutation are best addressed by a global approach involving microarray and proteomic analyses which are proposed. The results of the proposed research will lead to a greater understanding of how LasB, an important virulence factor that is crucial in host tissue exploitation, also contributes to surface-associated motility, biofilm formation and QS regulation in this bacterium.

描述(由申请人提供)：铜绿假单胞菌是一种普遍存在的重要的机会致病菌，具有令人印象深刻的毒力因子。弹性蛋白酶是一种由lasB基因编码的金属蛋白酶，通过降解或灭活组织和免疫系统组件而导致毒力。LasB的表达既需要LAS群体感应(QS)系统，也需要PQS。人们对弹性蛋白酶在这种细菌的生命中所起的作用知之甚少。我们实验室最近发现的证据表明，lasB突变细胞在抽动和聚集运动方面都严重不足，这是我们实验室首次提出的证据。表面结合运动对于细菌种群的生存和扩散是必不可少的，并在生物膜的形成中起着决定性的作用。这项拟议的研究将探讨弹性蛋白酶影响这两种运动形式的机制(S)。抽搐运动依赖于PILT介导的IV型菌毛回缩。在lasB突变细胞中，菌毛回缩受到抑制，因此我们的研究将集中在lasB影响菌毛回缩的机制上。群居运动需要鞭毛和鼠李糖脂。在lasB突变细胞上，鞭毛的数量和位置发生了变化。此外，lasB突变细胞产生少量的C4-高丝氨酸内酯(HSL)。鼠李糖脂、花青素和吡喃素的产生都是由以C4-HSL为同源信号的Rh_1群体感应系统控制的。LasB基因本身受QS调控，这项拟议的研究试图确定弹性蛋白酶如何影响铜绿假单胞菌AHL的产生。LasB突变的多效性效应最好通过涉及微阵列和蛋白质组学分析的全球方法来解决，这是提出的。拟议的研究结果将有助于更好地理解LasB，一个在宿主组织开发中至关重要的重要毒力因子，也有助于这种细菌的表面相关运动性、生物膜的形成和QS调节。

项目成果

Conformationally constrained peptides from CD2 to modulate protein-protein interactions between CD2 and CD58.

• DOI: 10.1021/jm200004e
• 发表时间: 2011-08-11
• 期刊: JOURNAL OF MEDICINAL CHEMISTRY
• 影响因子: 7.3
• 作者: Gokhale, Ameya;Weldeghiorghis, Thomas K.;Taneja, Veena;Satyanarayanajois, Seetharama D.
• 通讯作者: Satyanarayanajois, Seetharama D.