A quorum-sensing-regulated protein controls cell surface alteration in S. pyogenes

群体感应调节蛋白控制化脓性链球菌细胞表面的改变

基本信息

批准号：
10212951
负责人：
Artemis Gogos
金额：
$ 4.46万
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：
2018
资助国家：
美国
起止时间：
2018-08-16 至 2022-05-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10212951
关键词：
Acute Acute Pharyngitis Affect Antibiotic Resistance Antibodies Attention Bacteria Behavior Binding Biological Assay Cell Wall Cell surface Cells Charge Chemicals Communication Communities Data Detection Disease Electrostatics Enzyme-Linked Immunosorbent Assay Fluorescence Microscopy Fostering Gene Expression Genes Genetic Transcription Goals Homologous Gene Human Hydrophobicity IL8 gene Immune Evasion Immune response Immune system Impetigo Infection Knowledge Lead Masks Measures Mediating Microbial Biofilms Modification Molecular Muramidase Mus Necrotizing fasciitis Organism Pathogenicity Pathway interactions Peptide Signal Sequences Peptidoglycan Phenotype Physiological Population Preparation Production Proteins Reporter Research Resistance Reverse Transcriptase Polymerase Chain Reaction STC1 gene Scarlet Fever Severities Signal Transduction Streptococcus Streptococcus pyogenes Surface System Testing Therapeutic Time Up-Regulation Virulent Work base experimental study extracellular host colonization human disease in vivo in vivo imaging system inhibitor/antagonist insight intercellular communication lipoteichoic acid microbial mouse model novel pathogen quorum sensing receptor response success tissue culture

项目摘要

PROJECT SUMMARY Streptococcus pyogenes, also known as Group A Streptococcus (GAS), is a gram-positive pathogen that, in its virulent state, is responsible for a variety of human diseases ranging from acute pharyngitis, impetigo, scarlet fever, and necrotizing fasciitis. In addition to its contribution to these disease states, the bacterium is also asymptomatically colonizing up to 35% the population, and this colonization state remains its major reservoir for survival. Our group has characterized a novel quorum sensing system in S. pyogenes termed the Rgg2/3 pathway which consists of two transcriptional regulators, an activator (Rgg2) and a repressor (Rgg3) that are modulated by two short hydrophobic peptide signals (SHPs). The Rgg 2/3 circuit regulates a small secreted protein, Stc, that induces increased biofilm formation and enhanced lysozyme resistance. Both of these phenotypes are indicative of alterations to the cell surface of the bacterium, and we have recently shown that the positively-charged Stc protein is secreted to the cell surface where it associates with surface moieties and makes the surface more positively charged. This proposal seeks to confirm the surface moieties with which Stc associates, and determine whether or not they are obscurred from detection by the host by Stc’s presence. We have preliminary data showing that Stc expression leads to decreased activation of NFκB, which leads us to believe the Stc-expressing bacteria will have a colonization advantage. A murine model of intranasal colonization will be carried out to confirm this colonization advantage as well as examine the NFκB response in vivo. Success of this project work will allow us to explore use of already identified therapeutics that disrupt Rgg2/3 QS in order to eliminate bacteria in a colonizing state.

项目概要化脓性链球菌，也称为 A 组链球菌 (GAS)，是一种革兰氏阳性病原体，在其剧毒状态，导致多种人类疾病，包括急性咽炎、脓疱疮、猩红热发烧和坏死性筋膜炎除了导致这些疾病状态外，该细菌还具有以下作用：无症状地殖民了高达 35% 的人口，而这种殖民状态仍然是其主要的储存库我们的研究小组在化脓性链球菌中发现了一种新型群体感应系统，称为 Rgg2/3。该途径由两个转录调节因子组成，即激活子 (Rgg2) 和阻遏子 (Rgg3) 由两个短疏水肽信号 (SHP) 调节 Rgg 2/3 电路调节一个小的分泌蛋白。蛋白质 Stc，可诱导生物膜形成增加并增强溶菌酶抵抗力。表型表明细菌细胞表面的改变，我们最近表明带正电荷的 Stc 蛋白被分泌到细胞表面，与表面部分结合，使表面带更多正电该提案旨在确认 Stc 所带有的表面部分。同事，并确定他们是否因 Stc We 的存在而被宿主检测到。初步数据显示 Stc 表达导致 NFκB 激活减少，这使我们相信表达 Stc 的细菌将具有定植优势鼻内定植的小鼠模型。将进行以确认这种定植优势并检查体内 NFκB 反应是否成功。该项目工作的一部分将使我们能够探索使用已经确定的破坏 Rgg2/3 QS 的疗法，以便消除处于定植状态的细菌。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Modeling Streptococcus pyogenes Pharyngeal Colonization in the Mouse.

化脓性链球菌在小鼠咽部定植的建模。

DOI：
发表时间：
2019
期刊：
影响因子：
0
作者：
Gogos, Artemis;Federle, Michael J
通讯作者：
Federle, Michael J

A Quorum Sensing-Regulated Protein Binds Cell Wall Components and Enhances Lysozyme Resistance in Streptococcus pyogenes.

群体感应调节蛋白结合细胞壁成分并增强化脓性链球菌的溶菌酶抗性。

DOI：
发表时间：
2018-06-01
期刊：
影响因子：
3.2
作者：
Gogos, Artemis;Jimenez, Juan Cristobal;Chang, Jennifer C;Wilkening, Reid V;Federle, Michael J
通讯作者：
Federle, Michael J

Colonization of the Murine Oropharynx by Streptococcus pyogenes Is Governed by the Rgg2/3 Quorum Sensing System.

化脓性链球菌在小鼠口咽部的定植受 Rgg2/3 群体感应系统控制。