权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Pseudomonas aeruginosa quorum sensing

铜绿假单胞菌群体感应

基本信息

批准号：
10319599
负责人：
Ajai Dandekar
金额：
$ 31.1万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-01-05 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10319599
关键词：
Affinity Antibiotics Bacteria Behavior Biochemical Biological Biology Cell Communication Cell Density Cells Characteristics Chronic Clinical Code Collection Communication Methods Complex Cooperative Behavior Cystic Fibrosis Data Deterioration Disease Elements Environment Gene Expression Gene Targeting Genes Genetic Genetic Diseases Genome Goals In Vitro Infection Laboratories Lung Lung infections Mediating Modeling Molecular Morbidity - disease rate Mutation N-butyrylhomoserine lactone Organism Patients Peptide Hydrolases Persons Plague Population Population Control Production Pseudomonas aeruginosa Pseudomonas aeruginosa infection Pulmonary Cystic Fibrosis Regulation Regulon Reporting Respiratory Tract Infections Role Signal Transduction Source System Transcriptional Regulation Virulence Virulence Factors Work chronic infection cystic fibrosis infection cystic fibrosis patients experimental study homoserine lactone human disease human pathogen intercellular communication interest mortality mutant opportunistic pathogen preservation prevent quorum sensing response restraint social therapeutic development transcription factor

项目摘要

Project Summary Quorum sensing (QS) is a broadly distributed intercellular communication method used by bacteria to coordinate group activities. The opportunistic human pathogen Pseudomonas aeruginosa uses QS to regulate the production of numerous secreted products that include virulence factors, antibiotics, and proteases. The ability of P. aeruginosa to alter its behavior as a group contributes to the difficulty of treating this bacterium in diseases such as cystic fibrosis, in which it establishes chronic airway infections. In P. aeruginosa, QS is mediated in part by the transcription factors LasR and RhlR, which respond to acyl-homoserine lactone signals. In laboratory strains, LasR regulates RhlR, and together they control the transcription of hundreds of genes. LasR mutants are common in CF (although RhlR mutants are not usually observed) implying inactivation of QS in these isolates. However, in many P. aeruginosa isolates from cystic fibrosis, RhlR activity is not dependent on LasR and many LasR-null isolates still engage in acyl-homoserine lactone QS. The presence of active RhlR QS in these strains implies that QS is important for the regulation of certain factors within the CF lung. This proposal uses a large collection of P. aeruginosa isolates from cystic fibrosis patients to explore adaptations P. aeruginosa makes to preserve QS despite lasR mutation. The experiments described in this proposal ask: 1) what are the genes regulated by QS transcription factors and what is the “core” QS regulon of clinical isolates; 2) what are the genetic changes that allow for LasR-independent RhlR activation in these clinical isolates and what are the direct gene targets of RhlR?; and 3) what are the molecular mechanisms that prevent RhlR mutants from emerging in populations of P. aeruginosa? The answers to these questions will give a more complete picture of QS in clinical P. aeruginosa, and guide efforts to target QS or QS-regulated genes to manage and treat bacterial populations in human disease.

项目摘要群体感应（QS）是细菌广泛分布的细胞间通讯方式，协调小组活动。人类机会致病菌铜绿假单胞菌使用QS调节产生大量分泌产物，包括毒力因子、抗生素和蛋白酶。的铜绿假单胞菌作为一个群体改变其行为的能力导致了治疗这种细菌的困难，疾病，如囊性纤维化，其中它建立慢性气道感染。在铜绿假单胞菌中，QS为部分由转录因子LasR和RhlR介导，其响应于酰基高丝氨酸内酯信号.在实验室菌株中，LasR调节RhlR，并且它们一起控制数百个转录因子的转录。基因. LasR突变体在CF中是常见的（尽管RhlR突变体通常不被观察到），这意味着这些分离株中QS的失活。然而，在来自囊性纤维化的许多铜绿假单胞菌分离物中，RhlR活性降低。不依赖于LasR，并且许多LasR无效分离物仍然参与酰基高丝氨酸内酯QS。这些菌株中活性RhlR QS的存在意味着QS对于某些细胞的调节是重要的。 CF肺内的因素。该提案使用了大量从囊性纤维化中分离的铜绿假单胞菌患者探索铜绿假单胞菌在lasR突变的情况下保持QS的适应性。实验在这个建议中描述的问题：1）QS转录因子调控的基因是什么，临床分离株的“核心”QS调节子; 2）允许LasR非依赖性RhlR的遗传变化是什么在这些临床分离株中的活化以及RhlR的直接基因靶点是什么？（3）什么是防止RhlR突变体在铜绿假单胞菌群体中出现的分子机制？对这些问题的回答将更全面地了解QS在临床铜绿假单胞菌中的作用，致力于靶向QS或QS调节基因以管理和治疗人类疾病中的细菌群体。