Physiology of S aureus Vancomycin Resistance

金黄色葡萄球菌万古霉素耐药性的生理学

• 批准号: 6358170
• 负责人: BRIAN JAMES WILKINSON
• 金额: $ 12.3万
• 依托单位: ILLINOIS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-15 至 2005-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6358170
• 关键词: Staphylococcus aureus; bacterial genetics; biological transport; cell wall; drug resistance; microorganism culture; microorganism metabolism; peptidoglycan; sodium ion; teichoate; vancomycin

DESCRIPTION (provided by applicant): It is imperative that serious Staphylococcus aureus diseases such as bacteremia and infectious endocarditis are treated aggressively with effective antimicrobial agents. These diseases had mortality rates of 80 and 100 percent respectively in the pre-antibiotic era. Most hospital strains of S. aureus are now methicillin-resistant (MRSA), and such strains are typically resistant to multiple other antibiotics. The glycopeptide antibiotic vancomycin was the sole remaining antibiotic to which S. aureus remained uniformly susceptible. Recently. vancomycin-resistant strains have arisen in patients during long-term vancomycin therapy (so called glycopeptide-intermediate susceptible S. aureus or GISA strains). It is imperative that we understand the mechanism of vancomycin resistance in such strains. Vancomycin-resistant strains have been step selected in my laboratory. It is likely that the resistance mechanism involves several mutations and is multifaceted. I propose to study the mechanism of S. aureus vancomycin resistance in laboratory and clinical strains. I will study the composition and structure of peptidoglycan, and teichoic acid and lipoteichoic acid in GISA strains, and attempt to understand the mechanism of decreased autolytic activity observed in such strains. Cell wall alterations appear to be involved in vancomycin resistance. I will attempt to understand the increased NaC1-sensitivitv of GISA strains through studying the accumulation of compatible solutes. and whether Na+ ions accumulate intracellularly to growth inhibitory levels upon NaCl stress. Limited studies toward understanding the genetic basis of vancomycin will be undertaken. Nucleotide sequence analysis of cloned selected genes that physiological studies indicate may be altered in GISA strains will be carried out. It is expected that these studies will lead to improved methods for the control of methicillin-resistant and vancomycin-resistance S. aureus infections, and form the basis for development of novel antistaphylococcal agent.

描述（由申请人提供）：必须严重 金黄色葡萄球菌病如菌血症和感染性心内膜炎 用有效的抗菌剂积极治疗。这些疾病 在使用抗生素之前， 时代大多数医院菌株的S。金黄色葡萄球菌现在是耐甲氧西林的（MRSA）， 并且这些菌株通常对多种其它抗生素具有抗性。的 糖肽抗生素万古霉素是唯一剩下的抗生素， S.金黄色葡萄球菌仍然一致敏感。最近耐万古 在长期万古霉素治疗（所谓的万古霉素疗法）期间， 糖肽中间体敏感S.金黄色葡萄球菌或GISA菌株）。是 我们必须了解万古霉素耐药的机制， 菌株本实验室对万古霉素耐药菌株进行了逐步筛选。 耐药机制可能涉及几种突变， 多方面的本文拟对S.金黄色万古霉素 实验室和临床菌株的耐药性。我会研究这篇作文， GISA中肽聚糖、磷壁酸和脂磷壁酸结构 菌株，并试图了解减少自溶的机制， 在这些菌株中观察到的活性。细胞壁的改变似乎与 万古霉素耐药性我会努力去理解 GISA菌株的NaCl敏感性通过研究积累 相容的溶质。以及Na+离子是否在细胞内积累以促进生长 抑制水平。有限的研究，以了解 万古霉素的遗传基础。的核苷酸序列分析 克隆了生理学研究表明可能会改变的基因， 将进行GISA菌株。预计这些研究将导致 涉及用于控制甲氧西林抗性的改进方法， 耐万古霉素S.金黄色葡萄球菌感染，并形成发展的基础 新的抗葡萄球菌药物

项目成果

Intact mutS in laboratory-derived and clinical glycopeptide-intermediate Staphylococcus aureus strains.

实验室来源和临床糖肽中间金黄色葡萄球菌菌株中的完整 mutS。

• DOI: 10.1128/aac.48.2.623-625.2004
• 发表时间: 2004
• 期刊: Antimicrobial agents and chemotherapy
• 影响因子: 4.9
• 作者: Muthaiyan,Arunachalam;Jayaswal,RadheshyamK;Wilkinson,BrianJ
• 通讯作者: Wilkinson,BrianJ