ALTERNATIVE APPROACHES FOR E FAECALIS INFECTIONS

超出所提供的空间。肠球菌是心内膜炎的3个最常见原因，仅次于链球菌和葡萄球菌，也是医院获得性感染的2-3个最常见原因，粪肠球菌是分离出的优势菌种。抗微生物药物耐药性可能会促进肠球菌在医院感染中的建立，并且肯定会使成功治疗患者变得更加困难，特别是心内膜炎患者。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方法。工作期间，先前资助的拨款确定和表征了一些反基因编码基因；多糖基因簇（epa）似乎影响小鼠的毒性；不同的粘附表型和一个似乎与粘附有关的基因ace；以及一个与辅助基因调控（agr）位点或葡萄球菌同源的基因位点，该基因位点参与粪肠球菌凝胶酶和sene蛋白酶的表达，也影响小鼠的毒力。在这个应用中，我们建议验证粪肠球菌a^r-like基因座调控gelE和sprE，并确定它们是否对毒力都很重要；研究这些基因在粪肠杆菌中的分布；并确定肠球菌的aerer样位点是如何被调节的，以及它是否像葡萄球菌的agr一样，调节其他基因。我们还计划(2)验证以下假设：Ace（肠球菌胶原蛋白的一种新描述的黏附）是我们所报道的黏附的原因，对毒性很重要；探索Ace的生产规律；并确定ace变异的分布和影响，确定ace是否在受粪肠杆菌感染的人（使用重组ace和患者血清）中引起抗体反应，以及感染期间产生的抗体或重组ace抗体是否具有保护作用。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，研究其调控，并进一步测试其对外来物质的粘附，毒力和保护的贡献。我们还将基于我们之前对粪肠球菌pyr基因的研究，探索一种利用反选择构建非极性dele^n突变体的系统，并探索有助于我们避免致命性模型的其他分析方法。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。网站性能 ======================================== 节结束 ===========================================

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===========================================