REGULATION OF MULTIDRUG RESISTANCE IN S AUREUS

金黄色葡萄球菌多重耐药性的调控

• 批准号: 7960226
• 负责人: JOHN E GUSTAFSON
• 金额: $ 4.26万
• 依托单位: NEW MEXICO STATE UNIVERSITY LAS CRUCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7960226
• 关键词: Amino Acids; Biomedical Research; Clinical; Computer Retrieval of Information on Scientific Projects Database; Disinfectants; Environment; Ethanol; Funding; Gel; Genes; Genetic Transcription; Grant; Hand; Heat-Shock Response; Hospitals; Institution; Investigation; Laboratories; Membrane Proteins; Multi-Drug Resistance; Mutation; New Mexico; Predisposition; Protein Denaturation; Regulation; Research; Research Personnel; Resistance; Resources; Source; Staphylococcus aureus; Starvation; United States National Institutes of Health; antimicrobial; arginyllysine; mutant; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We have completed the investigation of the response of "golden staph" (S. aureus) to ethanol (Eth). Eth is the active antimicrobial present in the numerous disinfectant hand gels which are often utlized often to reduce the spread of Staphylococcus aureus throughout hospital environments. Our finding support the efficacy of these hand gels by demonstrating that under laboratory conditions, S. aureus cannot become resistant to the ethanol concentrations in hand gels. The highest Eth inhibitory concentration uncovered among 106 clinical S. aureus strains was only 15% and Eth reduced susceptibility (EthRS) mutants step-selected to 15% Eth after ~3 months demonstrated only 1% Eth resistance increases, both levels well below the ethanol levels of hand gels (~60%). The Eth stimulon of two unrelated strains revealed dramatically increased heat shock gene transcription (e.g. clpB, groES, and groEL). Two hundred and fifty nine altered genes were shared between the Eth stimulon and the amino acid starvation stimulon. In support of this finding we found that the addition of certain single amino acids (e.g. arg, lys and leu) to Eth susceptibility broth, led to increased resistance to Eth in all strains investigated. From these findings we were able to conlcude that the Eth susceptibility variability among the strains and the creation of EthRS mutants demonstrates that genetic alteration(s) contribute to the expression of Eth susceptibility levels. Eth static and cidal activity may be due to amino acid starvation, as well as membrane and protein denaturation.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 我们已经完成了对“金葡萄球菌”（S. aureus）对乙醇（ETH）的响应的调查。 ETH是存在于众多消毒的手凝胶中的活性抗菌剂，通常会经常被UTLECLIT，以减少金黄色葡萄球菌在整个医院环境中的传播。我们的发现通过证明在实验室条件下，金黄色葡萄球菌不能对手凝胶中的乙醇浓度具有抗性来支持这些手凝胶的功效。在106个临床金黄色葡萄球菌菌株中发现的最高的ETH抑制浓度仅为15％，ETH降低了易感性（ETHR）突变体，后者逐步选择了〜3个月后，其ETH逐步选择至15％ETH，表现仅1％的ETH耐药性增加，这两种水平都远低于乙醇水平（〜60％）。 两种无关菌株的ETH刺激片揭示了热休克基因转录大大增加（例如CLPB，GROES和GROEL）。 在乙醇刺激和氨基酸饥饿刺激元之间共享了259个改变的基因。为了支持这一发现，我们发现将某些单个氨基酸（例如ARG，LYS和LEU）添加到ETH易感性肉汤中，导致对所有菌株的耐药性提高。从这些发现中，我们能够结合菌株之间的ETH易感性变异性和ETHRS突变体的创建表明，遗传改变（S）有助于ETH易感水平的表达。 ETH静态活性和CIDAL活性可能是由于氨基酸饥饿以及膜和蛋白质变性引起的。