MULTI-DRUG RESISTANCE IN STAPHYLOCOCCUS AUREUS CLINICAL ISOLATES

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 金黄色葡萄球菌是一种严重的人类病原体，是社区和临床环境中的公共卫生问题。然而，细菌对抗菌剂的耐药性降低了对由沙门氏菌引起的感染性疾病的化疗效果。金黄色葡萄球菌，特别是该细菌的多药耐药菌株。因此，这种耐药机制的知识将在控制耐药机制的努力中具有临床实用性，从而恢复化疗药物的有用性。本项目申请中提出的实验的长期目标是增强我们对多药外排泵操纵子及其转录调控系统在临床分离的甲氧西林耐药链球菌中的功能作用的理解。金黄色葡萄球菌（MRSA）和万古霉素中间体S.金黄色葡萄球菌（VISA）。核心假设是farABC编码的外排泵介导对夫西地酸和乙锭的耐药性，为临床耐药性的产生提供了支架，并且yycFG元件控制这些泵基因的转录，从而导致抗菌药物耐药性。这些假设的基本原理是，一旦多药外排泵和它们的转录控制系统之间的关系是已知的，那么就可以了解葡萄球菌对多种抗菌剂的耐药机制。预期的成果是，将为本科生和研究生以及博士后研究员的培训工作提供便利。转录调控的生理学研究将为细菌对严重的人类病原体中的抗菌剂耐药性的重要系统提供分子见解，这是社区和临床环境中的公共卫生问题。

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. The bacterium Staphylococcus aureus is a serious human pathogen and a public health concern in both community and clinical settings. Bacterial resistance to antimicrobial agents, however, reduces chemotherapeutic effectiveness against infectious diseases caused by S. aureus, and in particular, multi-drug resistant strains of this bacterium. Thus, knowledge of such resistance mechanisms would be of clinical utility in the efforts to control the mechanisms that confer resistance, thus restoring the usefulness of chemotherapeutics. The long term objectives of the experiments proposed in this project application are to enhance our understanding of the functional roles of the multidrug efflux pump operon and its transcriptional regulatory system in clinical isolates of methicillin resistant S. aureus (MRSA) and vancomycin intermediate S. aureus (VISA). The central hypotheses are that farABC-encoded efflux pumps mediate resistance to fusidic acid and ethidium, provide scaffolding for clinical resistance to arise, and that yycFG elements control transcription of these pump genes, thus contributing to antimicrobial drug resistance. The rationale for these hypotheses is that once the relationships are known between the multidrug efflux pumps and their transcriptional control systems, then insight will be gained regarding Staphylococcal resistance mechanisms to multiple antimicrobial agents. The expected outcomes are that the training efforts will be facilitated for undergraduates and graduates plus postdoctoral fellows. Physiological studies with transcriptional regulation will provide molecular insight into important systems for bacterial resistance to antimicrobial agents in a serious human pathogen that is a public health concern in both community and clinical settings.