Pseudomonas aeruginosa quorum sensing

铜绿假单胞菌群体感应

• 批准号: 10080743
• 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
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-05 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10080743
• 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; Plague; Population; Population Control; Production; Pseudomonas aeruginosa; Pseudomonas aeruginosa infection; Pulmonary Fibrosis; Regulation; Regulon; Reporting; 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

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 Quorum Sensing（QS）是细菌使用的广泛分布的细胞间通信方法 坐标组活动。 生产许多分泌的产品，包括病毒性因子，抗生素和蛋白酶 铜绿假单胞菌改变的能力是行为，因为一组有助于treas细菌的差异 诸如Cystem纤维化之类的疾病，其中建立了慢性气道感染。 部分由转录因子LASR和RHLR介导，对ACHL-HOMOSERINE内酯反应 信号在实验室菌株中，LASR调节RHL，并共同转录 基因。 但是，在许多铜绿假单胞菌中，QS灭活。 不依赖LASR，许多LASR无效的分离株静止静止雄氨酸内酯QS。 在这些菌株中存在主动rhr QS意味着QS对于某些人来说很重要 CF肺中的因素。 探索适应性铜绿假单胞菌的患者尽管进行了LASR突变 在此原始问题中描述的：1）QS转录因子定制的基因是什么？ 临床分离株的“核心”调节； 2） 这些临床分离株的激活以及什么ARET基因靶标？ 铜绿假单胞菌种群中出现的突变体的分子机制？ 这些问题的答案将使铜绿假单胞菌中QS的QS图片更加艰巨，并指导 靶向QS或QS注册基因以管理和治疗人类疾病中的双臂种群的努力。