REGULATION OF MULTIDRUG RESISTANCE IN S AUREUS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们已经完成了对“金黄色葡萄球菌”（S。金黄色葡萄球菌）转化为乙醇（Eth）。乙醚是存在于许多消毒洗手凝胶中的活性抗菌剂，通常用于减少金黄色葡萄球菌在整个医院环境中的传播。我们的发现支持这些手凝胶的功效，证明在实验室条件下，S。金黄色葡萄球菌不能对手部凝胶中的乙醇浓度产生抗性。在106株临床沙门氏菌中发现最高抑菌浓度的Eth。金黄色葡萄球菌菌株的耐药性仅为15%，并且在~3个月后对15%Eth逐步选择的Eth降低敏感性（EthRS）突变体仅表现出1%Eth抗性增加，这两个水平均远低于手工凝胶的乙醇水平（~60%）。 两个不相关菌株的Eth刺激子显示显著增加的热休克基因转录（例如clpB、groES和groEL）。 Eth刺激子和氨基酸饥饿刺激子之间共有259个改变的基因。为了支持这一发现，我们发现向Eth敏感性肉汤中添加某些单一氨基酸（例如，精氨酸、赖氨酸和亮氨酸）导致所有研究菌株对Eth的抗性增加。根据这些发现，我们能够得出结论，菌株之间的Eth易感性变异性和EthRS突变体的产生表明遗传改变有助于Eth易感性水平的表达。乙醚静态和杀菌活性可能是由于氨基酸饥饿，以及膜和蛋白质变性。

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.