MULTI-DRUG RESISTANCE IN STAPHYLOCOCCUS AUREUS CLINICAL ISOLATES

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。 金黄色葡萄球菌是一种严重的人类病原体，在社区和临床环境中都是一个公共卫生问题。然而，细菌对抗菌剂的耐药性降低了对金黄色葡萄球菌引起的传染病的化疗效果，特别是这种细菌的多重耐药菌株。因此，对这种耐药机制的了解将有助于临床控制产生耐药的机制，从而恢复化疗药物的有效性。本项目申请中提出的实验的长期目标是加强我们对多药外排泵操纵子及其转录调控系统在耐甲氧西林金黄色葡萄球菌(MRSA)和万古霉素中间金黄色葡萄球菌(VISA)临床分离株中的功能作用的理解。中心假说是，farABC编码的外排泵介导了对呋西地酸和乙锭的耐药性，为临床耐药的产生提供了支架，yycFG元件控制这些泵基因的转录，从而导致抗菌素耐药性。这些假说的基本原理是，一旦了解了多药外排泵及其转录调控系统之间的关系，就可以深入了解葡萄球菌对多种抗菌剂的耐药机制。预期的结果是，将促进本科生和研究生以及博士后研究员的培训工作。具有转录调控的生理学研究将提供对一种严重的人类病原体中细菌抗药性的重要系统的分子洞察，这种病原体在社区和临床环境中都是一个公共卫生问题。

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.