MECHANISMS OF GLYCOPEPTIDE RESISTANCE IN STAPHYLOCOCCI

描述（改编自申请人摘要）：葡萄球菌 细菌是医院感染的主要原因， 感染和毒素介导的综合征， 年龄糖肽类（GP）万古霉素（Vm）和替考拉宁（Tco）是 治疗耐甲氧西林的最可靠的替代品 葡萄球菌，这是耐β-内酰胺类和广谱 抗生素。因此，临床葡萄球菌的出现 敏感性降低、异源耐药和真耐药的分离株 对GPS的抵制已经令人担忧。研究人员的研究是 目的是确定葡萄球菌中Vm和Tco的耐药机制。 抗药性可能是复杂和多因素的，因此，需要 多方面的调查方法在这方面，他们建议， 表征抗Vm实验室的转座子（Tn）突变体 衍生的金黄色葡萄球菌分离株，并对 其他临床Vm和Tco耐药的S.金黄色葡萄球菌分离株， 凝固酶阴性的抗Vm S.溶血性分离株他们还计划 筛选从选择的糖肽制备的质粒文库， 插入物的耐药临床和实验室分离株， 在敏感的分离株中赋予Vm抗性，以确定 质粒插入物在介导抗性中的作用。他们也建议 通过全局、随机、 抗病和感病植物基因组DNA和mRNA的比较 限制性内切酶标记基因组扫描和mRNA差异分析 目的是比较GP抗性和敏感S.金黄色 分离株进行这些工作的决定将部分基于 通过Tn诱变和质粒文库的筛选， 他们还将确定PBP 2是否有作用， 在许多临床和实验室来源的抗Vm的 分离物，通过灭活pbpB基因并评估其对 耐药性和异源耐药性，并采用禽流感 S.金黄色葡萄球菌菌血症开始澄清一些重要问题 关于S.金黄色。这些研究将导致 了解葡萄球菌抵抗Gps的机制， 可以提供新的蛋白质靶点， 可用于治疗GP引起的葡萄球菌感染 耐药菌株

DESCRIPTION (Adapted from the Applicant's Abstract): Staphylococcal species are a leading cause of nosocomial infections and a variety of infections and toxin mediated syndromes that affect patients of all ages. The glycopeptides (GP) vancomycin (Vm) and teicoplanin (Tco) are the most reliable alternatives for treatment of methicillin-resistant staphylococci, which are resistant to beta-lactams and a wide spectrum of antibiotics. Therefore, the emergence of clinical staphylococcal isolates with decreased susceptibility, heteroresistance, and true resistance to Gps has been alarming. The investigators' studies are aimed at identifying Vm and Tco resistance mechanisms in staphylococci. Resistance is likely to be complex and multifactorial and, thus, require a multifaceted investigative approach. In this regard, they propose to characterize a transposon (Tn) mutant of a Vm-resistant laboratory derived Staphylococcus aureus isolate and to perform Tn mutagenesis on other clinical Vm- and Tco-resistant S. aureus isolates and on a coagulase negative Vm-resistant S. haemolyticus isolate. They also plan to screen plasmid libraries prepared from selected glycopeptide- resistant clinical and laboratory isolate(s) for inserts capable of conferring Vm-resistance in Vm-susceptible isolates to determine the role of the plasmid insert in mediating resistance. They also propose to identify glycopeptide resistance determinants by global, random comparisons of genomic DNA and mRNA from resistant and susceptible isolates by restriction landmark genomic scanning and mRNA differential display aimed at comparing GP-resistant and -susceptible S. aureus isolates. The decision to undertake these will be based in part on what was learned with Tn mutagenesis and screening of the plasmid libraries. They will also determine whether there is a role for PBP2, found in increased abundance in many clinical and laboratory derived Vm-resistant isolates, by inactivating the pbpB gene and evaluating its effect on resistance and heteroresistance in staphylococci and employ an avian model of S. aureus bacteremia to begin to clarify some important issues regarding GP-resistance in S. aureus. These studies should lead to an understanding of the mechanisms by which staphylococci resist Gps and may provide novel protein targets against which antimicrobial agents could be designed to treat staphylococcal infections caused by GP resistant isolates.