Bacillithiol metabolism in Staphylococcus aureus

金黄色葡萄球菌中的杆菌硫醇代谢

基本信息

批准号：
8469058
负责人：
MAMTA RAWAT
金额：
$ 10.02万
依托单位：
CALIFORNIA STATE UNIVERSITY FRESNO
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8469058
关键词：
Acetyl Coenzyme A Acetylcysteine Acids Actinobacteria class Amides Amidohydrolases Anabolism Antibiotic Resistance Antibiotics Bacillus (bacterium)Bacterial Infections Biochemistry Candidate Disease Gene Cell physiology Cells Chiroptera Cleaved cell Community-Acquired Infections Cyanobacterium Cysteine Deacetylase Deacetylation Development Disease Disulfides Drug Metabolic Detoxication Drug Targeting Drug resistance Enzyme Tests Enzymes Equilibrium Eukaryota Glutathione Goals Gram-Negative Bacteria Guanine + Cytosine Composition Human Infection Infectious Skin Diseases Inositol Life Ligation Malates Metabolism Molecular Weight Nosocomial Infections Organism Oxidation-Reduction Oxidoreductase Pathway interactions Pharmaceutical Preparations Phenotype Play Prevalence Production Reactive Nitrogen Species Reactive Oxygen Species Recombinant Proteins Recombinants Recycling Research Resistance Septicemia Source Staphylococcal Infections Staphylococcus aureus Stress Structure Sulfhydryl Compounds System Therapeutic Toxic Shock Syndrome Toxin Transferase Vancomycin Resistance Xenobiotics amidase coping drug development drug metabolism enzyme activity glycosyltransferase human NAT2 protein insight methicillin resistant Staphylococcus aureus mutant pathogen

项目摘要

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.

描述（由申请人提供）：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越来越多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应对这一问题。最近发现的代谢物杆菌硫醇 (BSH) 已被证明存在于金黄色葡萄球菌和芽孢杆菌属中，但在人类或其他高等生物中不存在。该研究的具体目的是鉴定和表征 BSH 代谢中涉及的酶，例如杆菌硫醇二硫化物还原酶，并阐明金黄色葡萄球菌 BSH 依赖的异生物质解毒途径。这些研究的结果将详细阐述 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。由于已知硫醇参与耐药性的发展，因此这项研究可以深入了解金黄色葡萄球菌的内在耐药性。