ALTERNATIVE APPROACHES FOR E FAECALIS INFECTIONS

超出所提供的空间。 肠球菌是心内膜炎的3种最常见原因，仅次于链球菌和葡萄球菌，也是医院获得性感染的2-3种最常见原因，粪肠球菌是分离的主要菌种。抗生素耐药性可能促进了肠球菌在医院感染中的建立，并无疑使成功治疗患者变得更加困难，特别是那些心内膜炎患者。该项目的中心假设是，通过更好地了解肠球菌，可以开发新的治疗或预防模式。在先前资助的研究期间，我们鉴定并鉴定了一些抗原编码基因;一个似乎影响小鼠毒力的多糖基因簇（epa）;不同的粘附表型和一个似乎参与粘附的基因ace;一个与辅助基因调节子（agr）基因座或参与表达大肠杆菌的葡萄球菌具有同源性的基因座。粪明胶酶和番泻叶蛋白酶也影响小鼠中的毒力。在本申请中，我们提出m来验证粪肠球菌a^r样基因座调节gelE和sprE，并确定是否所有基因对毒力都很重要;研究这些基因在粪肠球菌中的分布。并确定肠球菌AER样位点是如何调节的，以及它是否像葡萄球菌AGR一样调节其他基因。我们还计划（2）检验Ace（一种新发现的肠球菌胶原粘附分子）是引起肠球菌粘附的原因，并对肠球菌的毒力有重要影响;并确定ACE变化的分布和影响，如果Ace能激发人体内的抗体反应（使用重组Ace和患者血清），并且如果在感染期间产生的抗体或针对重组Ace的抗体是保护性的。在我们的第三个具体目标中，我们计划（3）确定多糖基因簇是否是最近描述的粘液样表型的原因，研究其调节，并进一步测试其对粘附外来物质、毒力和保护的贡献。我们还将探索一种利用反选择构建非极性缺失突变体的系统，该系统基于我们先前对粪肠球菌pyr基因的研究，并探索有助于我们避免致死模型的其他测定方法。我们希望这项工作的结果将为我们寻求预防、控制或对抗粪肠球菌感染的方法提供坚实的线索。性能现场=

EXCEED THE SPACE PROVIDED. Enterococci are the 3 most common cause of endocarditis, behind streptococci and staphylococci, and the 2-3 most common cause of hospital acquired infections, with Enterococcusfaecalis being the predominant species isolated. Antimicrobial resistance likely facilitatesthe establishment of enterococci in nosocomial infec- tions and certainly makes it more difficult to successfullytreat patients, particularly those with endocarditis. The central hypothesis of this project is that by better understanding enterococci, new therapeutic or preventative mo- dalities can be developed. Work during a previously funded grant identified and characterized a number of anti- gen encoding genes; a polysaccharide gene cluster (epa) that appears to influencevirulence in mice; different ad- herence 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 or staphylococci that is involved in expression of an E. faecalis gelati- nase and a senne protease that also influence virulence in mice. In this application, we propose m to verify that the E.faecalis a^r-like locus regulates gelE and sprE and determine if all are important for virulence;to investi- gate the distribution of these genes among E. faecalis; and to determine how the enterococcal aer-like locus is regulated and if it, like the staphylococcal agr, regulates other genes. We also plan (2) to test the hypothesis that Ace (a newly described adhesm for collagen of enterococci) is the cause of the adherence we haye 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 recombinantAce and patient sera) in- fected by E.faecalis and if antibody made during infection, or antibody to recombinant Ace, is protective. In our third specific aim, we 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. We will also explore a system for constructing non-polar dele^n mutants usingcoun- terselection, based on our prior work with the E.faecalis pyr genes, and to explore additionalassays thatwould help us avoid lethalitymodels. We hope that results from this work will provide solid leads in our quest for meth- ods to prevent, control, or combat E.faecalis infections. PERFORMANCE SITE ========================================Section End===========================================