Bacillithiol metabolism in Staphylococcus aureus

描述（由申请方提供）：耐甲氧西林金黄色葡萄球菌（MRSA）已成为危及生命的医院感染和日益增加的社区获得性感染的严重来源。由于我们目前对MRSA感染的治疗正在失去疗效，因此迫切需要新的抗生素来科普这一问题。最近发现的代谢产物，bacillithiol（BSH），已被证明存在于S。金黄色葡萄球菌和芽孢杆菌属，但在人类或其他高等生物中不存在。本研究的具体目的是鉴定和表征参与BSH代谢的酶，如杆菌硫醇二硫还原酶，并阐明S。金黄色葡萄球菌BSH依赖的外源性解毒途径。这些研究的结果将阐述BSH的功能，并将确定BSH代谢是否是葡萄球菌药物开发的合适靶点。由于巯基参与了耐药性的形成，这项研究可能有助于了解沙门氏菌的内在耐药性。金黄色。

DESCRIPTION (provided by applicant): Methicillin resistant Staphylococcus aureus (MRSA) has become a serious source of life-threatening hospital infections and increasingly community acquired infections. As our current treatments for MRSA infections are losing efficacy, there is an urgent need for new antibiotics to cope with this problem. A recently discovered metabolite, bacillithiol (BSH), has been shown to be present in S. aureus and Bacillus spp., but is absent in human or other higher organisms. The specific aims of the research are to identify and characterize enzymes involved in BSH metabolism, such as bacillithiol disulfide reductase, and to elucidate S. aureus BSH dependent xenobiotic detoxification pathways. The results of these studies will elaborate the functions of BSH and will establish whether BSH metabolism is a suitable target for staphylococcal drug development. As thiols are known to be involved in the development of drug resistance, this research may provide insight into intrinsic drug resistance in S. aureus.