Mechanisms of Pheromone-Controlled Lysozyme Resistance and Surface Display of Streptococcus pyogenes

化脓性链球菌信息素控制的溶菌酶抗性和表面展示机制

基本信息

批准号：
10054149
负责人：
MICHAEL J FEDERLE
金额：
$ 39.98万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2022-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10054149
关键词：
Accounting Adhesives Affect Amidohydrolases Aminoglycosides Animal Model Antibiotics Appearance Bacteria Bacterial Adhesins Behavior Beta-N-Acetylglucosaminidase Binding Biochemical Cell Aggregation Cell Wall Cell surface Cells Chemicals Communicable Diseases Communication Communities Cysteine Cytokine Signaling Data Development Disease Outbreaks Enzyme Inhibitor Drugs Enzymes Epithelial Cells Fibronectins Histidine Human body Hydrolase Hydrophobicity Immune Immune response Immunologic Surveillance Invaded Lead Life Style Mediating Microbial Biofilms Muramidase N-Acetylmuramoyl-L-alanine Amidase Nutrient Pathway interactions Peptide Hydrolases Peptides Peptidoglycan Perception Periodicity Phenotype Pheromone Pheromone Receptors Physiological Predisposition Production Property Proteins Recombinant Proteins Regulation Regulatory Pathway Resistance Signal Transduction Streptococcus pyogenes Structural Protein Surface Testing Therapeutic Toxin Virulent experimental study host colonization immunoregulation in vivo pathogen pathogenic bacteria quorum sensing small molecule social

项目摘要

Project Summary/Abstract Little is understood about the physiological or regulatory factors of Streptococcus pyogenes that enable switching between its commensal-like and virulent states. This proposal describes experimental approaches that seek to continue defining and characterizing quorum-sensing regulatory pathways that correspond to phenotypes consistent with the avirulent lifestyle of Streptococcus pyogenes (Group A Streptococcus; GAS). The quorum sensing network in Streptococcus pyogenes utilizing short hydrophobic peptide (SHP) pheromones and the pheromone receptors Rgg2 and Rgg3 regulates several phenotypes, including biofilm development, cell aggregation, aminoglycoside susceptibility, and lysozyme resistance, by an unknown mechanism. Our studies indicate that each of these phenotypes depend upon the expression of a small protein of unknown function. We hypothesize that this protein, referred to as StcB, is an inhibitor of an enzyme(s) that targets peptidoglycan bonds of the cell wall. Additional studies indicate the target of StcB is a murein hydrolase enzyme, called Isp, that contains cysteine and histidine-dependent amidohydrolase/peptidase (CHAP) and acetylglucosaminidase domains. Governance of StcB and Isp by the Rgg2/3 quorum sensing pathway accounts for significant changes to the bacterial cell surface, resulting in differential attachment to fibronectin and epithelial cells, and differential immuno- modulatory activities. This proposal seeks to elucidate the mechanisms by which StcB and Isp enzymes account for biochemical changes to the surface of S. pyogenes, how these changes lead to differential activity of surface structures and proteins, and how these changes affect the ability of S. pyogenes to colonize the host and modulate immune activities.

项目概要/摘要人们对化脓性链球菌的生理或调节因素知之甚少。使其能够在共生状态和毒性状态之间切换。该提案描述了寻求继续定义和表征群体感应的实验方法与无毒生活方式一致的表型相对应的调节途径化脓性链球菌（A 组链球菌；GAS）。群体感应网络化脓性链球菌利用短疏水肽 (SHP) 信息素和信息素受体 Rgg2 和 Rgg3 调节多种表型，包括生物膜发育、细胞聚集、氨基糖苷敏感性和溶菌酶抗性，其机制未知。我们的研究表明，这些表型中的每一个都取决于以下小蛋白的表达：未知功能。我们假设这种称为 StcB 的蛋白质是一种抑制剂针对细胞壁肽聚糖键的酶。其他研究表明目标 StcB 是一种胞壁质水解酶，称为 Isp，含有半胱氨酸和组氨酸依赖性酰胺水解酶/肽酶 (CHAP) 和乙酰氨基葡萄糖苷酶结构域。 StcB 和 Isp 的治理 Rgg2/3 群体感应途径导致细菌细胞表面发生显着变化，导致对纤连蛋白和上皮细胞的不同附着，以及不同的免疫调节活动。该提案旨在阐明 StcB 和 Isp 的机制酶解释了化脓性链球菌表面的生化变化，这些变化如何导致表面结构和蛋白质的差异活性，以及这些变化如何影响 S. 化脓菌定植宿主并调节免疫活动。

项目成果

期刊论文数量（36）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Redundant group a streptococcus signaling peptides exhibit unique activation potentials.

冗余a组链球菌信号肽表现出独特的激活潜力。

DOI：
发表时间：
2013-09
期刊：
影响因子：
3.2
作者：
LaSarre, Breah;Chang, Jennifer C;Federle, Michael J
通讯作者：
Federle, Michael J

Quorum Sensing Regulation of Competence and Bacteriocins in Streptococcus pneumoniae and mutans.

肺炎链球菌和变形链球菌能力和细菌素的群体感应调节。

DOI：
发表时间：
2017-01-05
期刊：
影响因子：
3.5
作者：
Shanker, Erin;Federle, Michael J
通讯作者：
Federle, Michael J

One if by land, two if by sea: signalling to the ranks with CSP and XIP.

如果通过陆地，则为 1 个，如果通过海上，则为 2 个：通过 CSP 和 XIP 向部队发出信号。

DOI：
发表时间：
2012-10
期刊：
影响因子：
3.6
作者：
Federle, Michael J;Morrison, Donald A
通讯作者：
Morrison, Donald A

Multiple length peptide-pheromone variants produced by Streptococcus pyogenes directly bind Rgg proteins to confer transcriptional regulation.

化脓性链球菌产生的多长度肽信息素变体直接结合 Rgg 蛋白以赋予转录调节作用。

DOI：
发表时间：
2014-08-08
期刊：
影响因子：
0
作者：
Aggarwal, Chaitanya;Jimenez, Juan Cristobal;Nanavati, Dhaval;Federle, Michael J
通讯作者：
Federle, Michael J

Identification of Quorum-Sensing Inhibitors Disrupting Signaling between Rgg and Short Hydrophobic Peptides in Streptococci.

鉴定扰乱链球菌中 Rgg 和短疏水肽之间信号传导的群体感应抑制剂。

DOI：
发表时间：
2015-05-12
期刊：
影响因子：
6.4
作者：
Aggarwal, Chaitanya;Jimenez, Juan Cristobal;Lee, Hyun;Chlipala, George E;Ratia, Kiira;Federle, Michael J
通讯作者：
Federle, Michael J