QacA-mediated multidrug resistance and export in Staphylococcus aureus

QacA介导的金黄色葡萄球菌多药耐药性和输出

• 批准号: nhmrc : 153817
• 负责人: Prof Melissa Brown
• 金额: $ 29.18万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/qaca-mediated-multidrug-staphylococcus-aureus/94730
• 关键词: QacA; mediated; multidrug; resistance; export

Strains of the pathogenic bacterium Staphylococcus aureus (Golden Staph) which are resistant to almost all available anti-staphylococcal agents are responsible for serious infections among hospitalised patients; in some hospitals such outbreaks reach epidemic proportions. In these bacteria, resistance has emerged to all classes of antimicrobial agents, including antibiotics and antiseptics-disinfectants commonly used in the hospital environment, largely due to the acquisition of resistance determinants. These determinants encode for proteins which provide the bacterial cell with a range of different biochemical mechanisms to evade antibiotic chemotherapy. Specifically, this project seeks to increase our understanding of proteins which confer resistance by pumping a variety of structurally-dissimilar antimicrobials out of the bacterial cell. Proteins which recognise such a broad spectrum of compounds are called multidrug resistance proteins and present a disturbing clinical threat since the acquisition of one such system by a cell may simultaneously decrease its susceptibility to a number of antimicrobials. Similar multidrug pumps are widespread in nature and are credited for resistance to antibiotics and other chemotherapeutic drugs in many pathogenic organisms, such as the bacteria responsible for tuberculosis, and in human cancer cells. In this project, we aim to characterise the QacA multidrug resistance protein which is involved in pumping many different antimicrobial compounds from staphylococcal cells. We will identify the regions of the QacA multidrug resistance protein which bind the compounds and examine how the protein expels them to give resistance. These studies are a prerequisite for the design of more effective antibacterial compounds able to bypass these drug resistance pumps, and will also provide fundamental knowledge applicable to the problem of multidrug resistance in other infectious diseases and cancer.

致病性金黄色葡萄球菌（金黄色葡萄球菌）菌株对几乎所有可用的抗葡萄球菌药物均具有耐药性，是造成住院患者严重感染的原因；在一些医院，此类疫情已达到流行病的程度。在这些细菌中，对所有类别的抗菌剂都出现了耐药性，包括医院环境中常用的抗生素和防腐消毒剂，这主要是由于获得了耐药性决定因素。这些决定簇编码的蛋白质为细菌细胞提供一系列不同的生化机制来逃避抗生素化疗。具体来说，该项目旨在通过从细菌细胞中泵出各种结构不同的抗菌剂来增加我们对赋予耐药性的蛋白质的理解。识别如此广泛的化合物的蛋白质被称为多药耐药性蛋白质，并且呈现出令人不安的临床威胁，因为细胞获得这样的系统可能同时降低其对多种抗菌剂的敏感性。类似的多药泵在自然界中广泛存在，并被认为是许多病原生物体（例如导致结核病的细菌）和人类癌细胞对抗生素和其他化疗药物产生耐药性的原因。在这个项目中，我们的目标是表征 QacA 多药耐药蛋白，该蛋白参与从葡萄球菌细胞中泵出许多不同的抗菌化合物。我们将确定 QacA 多药耐药蛋白中与化合物结合的区域，并检查该蛋白如何驱逐它们以产生耐药性。这些研究是设计能够绕过这些耐药泵的更有效抗菌化合物的先决条件，并且还将提供适用于其他传染病和癌症的多药耐药性问题的基础知识。