ALTERNATIVE APPROACHES FOR E FAECALIS INFECTIONS

粪肠球菌感染的替代方法

• 批准号: 6532827
• 负责人: BARBARA E MURRAY
• 金额: $ 33.54万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6532827
• 关键词: Enterococcus; Streptococcus infection; adhesin; bacterial genetics; bacterial polysaccharides; cell adhesion; collagenase; extracellular matrix; gene deletion mutation; gene induction /repression; gene mutation; laboratory mouse; microorganism culture; serine proteinases; virulence

DESCRIPTION (Adapted from the Applicant's Abstract): Enterococci are the 3rd most common cause of endocarditis, behind streptococci and staphylococci, and the 2nd or 3rd most common cause of hospital acquired infections, with Enterococcus faecalis being the predominant species isolated. Antimicrobial resistance likely facilitates the establishment of enterococci in nosocomial infections and certainly makes it more difficult to successfully treat patients, particularly those with endocarditis. The central hypothesis of this project is that by better understanding enterococci, new therapeutic or preventative modalities can be developed. Work during a previously funded grant identified and characterized a number of antigen encoding genes; a polysaccharide gene cluster (epa) that appears to influence virulence in mice; different adherence phenotypes, and a gene, ace, that appears to be involved in adherence; and a gene locus with homology to the accessory gene regulator (agr) locus of staphylococci that is involved in expression of an E. faecalis gelatinase and a serine protease that also influence virulence in mice. In this application, the investigators propose (1) to verify that the E. faecalis agr-like locus regulates gelE and sprE and determine if all are important for virulence; to investigate the distribution of these genes among E. faecalis; and to determine how the enterococcal agr-like locus is regulated and if it, like the staphylococcal agr, regulates other genes. They also plan (2) to test the hypothesis that Ace (a newly described adhesin for collagen of enterococci) is the cause of the adherence we have reported and is important for virulence; to explore the regulation of Ace production; and to determine the distribution and effect of variations in ace, if Ace elicits an antibody response in humans (using recombinant Ace and patient sera) infected by E. faecalis and if antibody made during infection, or antibody to recombinant Ace, is protective. In their third specific aim, they plan (3) to establish if the polysaccharide gene cluster is the cause of a recently described mucoid phenotype, to study its regulation, and to further test its contribution to adherence to foreign material, virulence and protection. They will also explore a system for constructing non-polar deletion mutants using counter-selection based on their prior work with the E. faecalis pyr genes, and to explore additional assays that would help to avoid lethality models. The investigators hope that results from this work will provide solid leads in the quest for methods to prevent, control, or combat E. faecalis infections.

描述（改编自申请人的摘要）：肠球菌是第三种 心内膜炎的最常见原因，仅次于链球菌和葡萄球菌， 医院获得性感染的第二或第三常见原因，其中 粪肠球菌是分离的优势菌种。抗菌 耐药性可能促进了医院内肠球菌的建立 感染，当然使它更难成功地治疗 患者，尤其是心内膜炎患者。这个问题的核心假设是 通过更好地了解肠球菌，新的治疗或 可以制定预防措施。在以前资助的赠款期间工作 鉴定和表征了许多抗原编码基因; 多糖基因簇（epa）似乎影响小鼠的毒力; 不同的粘附表型，以及一个基因，ace，似乎参与了 粘附;以及与辅助基因调节子（agr）具有同源性的基因位点 葡萄球菌的一个基因座，该基因座参与表达E.粪 明胶酶和丝氨酸蛋白酶也会影响小鼠的毒力。在这 应用，研究者建议（1）验证E.粪 agr样基因座调节gelE和sprE，并确定是否都是重要的， 研究这些基因在大肠杆菌中的分布。粪便; 并确定肠球菌agr样基因座是如何被调节的， 就像葡萄球菌的AGR一样，调节其他基因。他们还计划（2）测试 Ace（一种新发现的肠球菌胶原粘附素） 是我们报告的粘附的原因，对毒力很重要; 探索Ace生产的规律;并确定分配 以及如果Ace在人体中引起抗体应答， （使用重组Ace和患者血清）感染E.粪便，如果 在感染期间产生的抗体或重组Ace的抗体具有保护性。 在他们的第三个具体目标中，他们计划（3）确定多糖是否 基因簇是最近描述的粘液样表型的原因，研究 它的监管，并进一步测试其对遵守外国 材料、毒性和保护。他们还将探索一个系统， 使用基于它们的反向选择构建非极性缺失突变体， 与E的前期工作faecalis pyr基因，并探索其他检测方法 这将有助于避免致命性模型。研究人员希望， 从这项工作将提供坚实的线索，在寻求方法，以防止， 控制或战斗E。粪便感染