STREPTOCOCCUS PYOGENES--CLONAL ANALYSIS OF VIRULENCE

化脓性链球菌——毒力克隆分析

基本信息

批准号：
6169738
负责人：
EDWARD A GRAVISS
金额：
$ 16.45万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-12-01 至 2001-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6169738
关键词：
Streptococcus infection Streptococcus pyogenes bacterial cytopathogenic effect bacterial genetics bacterial proteins endopeptidases exotoxins gene mutation genetic strain microorganism culture microorganism population study polymerase chain reaction protein structure function site directed mutagenesis tissue /cell culture transmission electron microscopy virulence

项目摘要

DESCRIPTION (Adapted from the applicant's abstract): Streptococcal pyrogenic exotoxin B (SpeB) is highly conserved among the group A streptococci (i.e., Streptococcus pyogenes), it has been shown that SpeB is cysteine protease and that it is important virulence factor in streptococcal pathogenesis (including data provided by the P.I. describing the relative virulence of isogenic pairs of SpeB producing and non-producing strains). Three studies will further address the role of SpeB in streptococcal virulence: 1) generation of site-specific mutants of speB, production of the altered SpeB proteins and determination of the enzymatic properties of the SpeB variants to continue ongoing structure-function analyses; 2) using purified SpeB variants (both naturally occurring and mutationally derived, in tissue culture experiments (using human umbilical vein epithelial cells) to probe the molecular pathophysiological processes induced by SpeB and including potential synergies between SpeB and the cytolytic toxin streptolysin O; 3) using transmission electron microscopy to determine if group A streptococci are internalized in culture and in episodes of human invasive disease. The critical data motivating these studies, and produced by the P.I.'s laboratory, is that SpeB can degrade host extracellular matrix proteins like fibronectin and vitronectin, cleaves and activates interleukin-1 beta and that immunization of mice with SpeB protects in intraperitoneal challenge experiments. The P.I. also proposes to explore in depth his own finding, recently published, that SpeB cleaves and activates a matrix metallo-protease produced by human endothelial cells.

描述（改编自申请人的摘要）：链球菌在A组中，热源外毒素B（SPEB）高度保守链球菌（即，化脓性链球菌），已经表明SPEB为半胱氨酸蛋白酶，它是链球菌中重要的毒力因子发病机理（包括描述相对的P.I.提供的数据 SPEB产生和非生产菌株的等源性对的毒力。三项研究将进一步解决SPEB在链球菌中的作用毒力：1）SPEB的位点特异性突变体的产生，生产 SPEB蛋白改变并确定的酶特性 SPEB变体继续进行持续的结构功能分析； 2）使用纯化的SPEB变体（自然发生和突变衍生，在组织培养实验中（使用人脐静脉上皮细胞）探测SPEB和SPEB诱导的分子病理生理过程包括SPEB和细胞溶解毒素之间的潜在协同作用链霉菌素O; 3）使用透射电子显微镜确定是否是否 A组链球菌在人类的培养和发作中被内在化侵入性疾病。促使这些研究的关键数据，并产生了 P.I.的实验室是SPEB可以降解宿主细胞外基质蛋白质如纤连蛋白和玻璃纤维，裂解和激活白介素-1β和用SPEB的小鼠免疫在腹膜内挑战实验。 P.I.还建议探索最近出版的他自己的发现，Speb裂解并激活了由人内皮细胞产生的基质金属蛋白酶。

项目成果

期刊论文数量（43）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

DNA fingerprinting of pathogenic bacteria by fluorophore-enhanced repetitive sequence-based polymerase chain reaction.

DOI：
发表时间：
1995
期刊：
Archives of pathology & laboratory medicine
影响因子：
4.6
作者：
James Versalovic;Vivek Kapur;T. Koeuth;G. Mazurek;T. Whittam;J. M. Musser;J. R. Lupski
通讯作者：
James Versalovic;Vivek Kapur;T. Koeuth;G. Mazurek;T. Whittam;J. M. Musser;J. R. Lupski

Non-congruent relationships between variation in emm gene sequences and the population genetic structure of group A streptococci.

emm 基因序列变异与 A 组链球菌群体遗传结构之间的非一致性关系。