ALTERNATIVE APPROACHES FOR E FAECALIS INFECTIONS

肠球菌是心内膜炎的三个最常见的原因，仅次于链球菌和葡萄球菌。 2-3医院获得性感染的最常见原因，以粪肠球菌为主 被隔离的物种。抗生素耐药性可能促进医院感染肠球菌的建立。 这无疑增加了成功治疗患者的难度，尤其是那些患有心内膜炎的患者。这个 该项目的中心假设是，通过更好地了解肠球菌，新的治疗或预防措施。 牙齿可以被开发出来。在先前资助的赠款期间的工作确定并表征了一些反 基因编码基因；一个似乎影响小鼠证据能力的多糖基因簇；不同的ad- 遗传表型和一个似乎与粘连有关的基因ace；以及一个与 参与粪肠球菌表达的辅助基因调节基因(AGR)基因座或葡萄球菌。 Nase和一种也影响小鼠毒力的Senne蛋白酶。在本应用程序中，我们建议使用m来验证 粪肠球菌A^R基因座调控GLE和Sprint E，并决定它们是否对毒力都重要； 确定这些基因在粪肠球菌中的分布；并确定肠球菌类Aer基因座是如何 如果它像葡萄球菌agr一样，调节其他基因。我们还计划(2)检验假设 ACE(一种新描述的肠球菌胶原蛋白粘附剂)是我们报道的粘连的原因。 对毒力很重要；探索Ace产生的调节；并确定其分布和影响 如果Ace在人类中引起抗体反应(使用重组Ace和患者血清)， 受粪肠球菌感染，感染期间产生的抗体或重组Ace抗体是否具有保护性。在我们的 第三个具体目标，我们计划(3)确定多糖基因簇是否是最近描述的 粘液表型，研究其调节，并进一步测试其对异物黏附的贡献， 毒性和保护性。我们还将探索一种构建非极性Dele^n突变体的系统。 三次选择，基于我们之前对粪肠球菌PYR基因的工作，并探索将 帮我们避开嗜睡症模特。我们希望这项工作的结果将为我们寻找冰毒提供可靠的线索- 用于预防、控制或抗击粪肠球菌感染的消耗臭氧层物质。

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.