Phase-variable gene expression in Pseudomonas aeruginosa

铜绿假单胞菌中的相变基因表达

基本信息

批准号：
7758222
负责人：
SIMON L DOVE
金额：
$ 35.86万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-02-01 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7758222
关键词：
Antibiotics Bacteria Communities Cystic Fibrosis Gene Cluster Gene Expression Gene Targeting Genes Gram-Negative Bacteria Growth Human Immune response Light Lung Microbial Biofilms Molecular Morbidity - disease rate Organism Phase Play Process Proteins Pseudomonas aeruginosa Repression Resistance Role Structure Surface Testing Virulence Virulence Factors base cystic fibrosis patients mortality pathogen rho termination factor transcription termination

Antibiotics Bacteria Communities Cystic Fibrosis Gene Cluster Gene Expression Gene Targeting Genes Gram-Negative Bacteria Growth Human Immune response Light Lung Microbial Biofilms Molecular Morbidity - disease rate Organism Phase Play Process Proteins Pseudomonas aeruginosa Repression Resistance Role Structure Surface Testing Virulence Virulence Factors base cystic fibrosis patients mortality pathogen rho termination factor transcription termination

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项目摘要

Pseudomonas aeruginosa is an important opportunistic pathogen of humans that is notorious for being the principal cause of morbidity and mortality in Cystic Fibrosis (CF) patients. In the chronically infected CF lung the organism persists as a biofilm¿a surface attached community of bacteria encased in a polymeric matrix. This biofilm mode of growth augments the resistance of P. aeruginosa to antibiotics and facilitates evasion of the host immune response. Prominent amongst those genes that play an important role in biofilm formation in P. aeruginosa are the cupA genes, which encode components of a putative fimbrial structure that facilitates surface- attachment. We have found that MvaT, a protein recently identified in P. aeruginosa as a global regulator of virulence gene expression, controls the phase-variable (i.e. ON/OFF) expression of the cupA fimbrial gene cluster. The proposed studies will determine how MvaT exerts this control. Our recent findings also implicate Rho, a transcription termination factor, in this same process. We therefore propose to explore the possibility that MvaT and Rho function synergistically to achieve efficient repression of phase-variable cupA gene expression. Moreover, we will attempt to elucidate the mechanism by which phase-variable cupA gene expression (the first of its kind documented in P. aeruginosa) actually occurs. We anticipate that these studies will illuminate the mechanism by which MvaT controls the expression of the cupA genes and, by extension, other MvaT-target genes that contribute to virulence. We anticipate further that these studies will also shed light on the molecular basis behind phase-variable gene expression in P. aeruginosa.

铜绿假单胞菌是人类的重要机会病原体，臭名昭著是囊性纤维化（CF）患者发病率和死亡率的主要原因。在慢性上受感染的CF肺持续存在为生物膜。聚合物矩阵。这种生长模式增强了铜绿假单胞菌对抗生素和促进宿主免疫反应的演变。在铜绿假单胞菌中生物膜形成中起重要作用的基因中的突出是 Cupa基因编码了推定的纤维化结构的组件，该结构促进了表面依恋。我们发现，MVAT是最近在铜绿假单胞菌中鉴定为全球调节剂MVAT 病毒基因表达，控制CUPA纤维化基因的相变（即开/关）表达簇。拟议的研究将确定MVAT如何施加此控制。我们最近的发现也在同一过程中实施RHO，是转录终止因子。因此，我们建议探索 MVAT和RHO协同功能以实现相变CUPA的有效表达的可能性基因表达。此外，我们将尝试阐明相变的CUPA基因的机制实际上发生了表达（铜绿假单胞菌中的第一个记录）。我们预计这些研究将阐明MVAT控制的机制 CUPA基因的表达，并扩展为有助于病毒的其他MVAT靶基因。我们预计这些研究还将阐明相变基因背后的分子基础铜绿假单胞菌的表达。