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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们完成了金黄色葡萄球菌(S.aureus)对乙醇(Eth)反应的研究。乙酸乙酯是存在于众多消毒剂手胶中的活性抗菌剂，通常用于减少金黄色葡萄球菌在医院环境中的传播。我们的发现证明，在实验室条件下，金黄色葡萄球菌不会对手胶中的乙醇浓度产生抗药性，从而支持了这些手胶的功效。在106株金黄色葡萄球菌临床分离株中发现的最高Eth抑制浓度仅为15%，而Eth减敏突变株在~3个月后逐步选择为15%Eth的突变株仅显示1%的Eth抗性增加，两者水平均远低于手胶的乙醇水平(~60%)。两个不相关菌株的Eth Stimulon显示热休克基因转录显著增加(例如ClpB、GroES和GroEL)。Eth Stimulon和氨基酸饥饿Stimulon共有259个改变的基因。为了支持这一发现，我们发现，在Eth敏感性肉汤中添加某些单一氨基酸(如Arg、Lys和Leu)，会导致所有研究菌株对Eth的抗性增加。根据这些发现，我们能够推断菌株之间的Eth敏感性变异和EtherRS突变体的产生表明遗传改变(S)有助于Eth敏感性水平的表达。ETH的静止和杀灭活性可能是由于氨基酸饥饿以及膜和蛋白质的变性所致。