Quinolone and multidrug resistance in Staphylococcus aureus

细菌外排泵在过表达时可引起多药耐药， 过表达的机制涉及一系列全局调节因子。金黄色葡萄球菌泵 诺拉、诺拉B和诺拉C可赋予对各种喹诺酮类抗菌药物的耐药性，沿着氯霉素 和一些染料。泵Tet38赋予对四环素类的抗性，并且泵AbcA赋予对普氏坦类的抗性 具有疏水侧链。已知两种全局转录调节因子MgrA和NorG， 在这些泵的表达中具有直接的调节作用。下文所述的工作 集中于i）定义控制泵表达的调节机制（包括复合物 各种调节因子的相互作用），ii）确定泵表达在S. 金黄色葡萄球菌在脓肿中生存，其最常见的感染原因，iii）确定环境 触发泵表达的信号，和iv）定义这些通常广谱的天然底物 泵，抗菌剂可能是附带底物。

Bacterial efflux pumps can cause multidrug resistance when overexpressed, and mutational mechanisms of overexpression have involved an array of global regulators. In Staphylococcus aureus pumps NorA, NorB, and NorC can confer resistance to various quinolone antimicrobials along with chloramphenicol and some dyes. Pump Tet38 confers resistance to tetracyclines, and pump AbcA confers resistance to plactams with hydrophobic side-chains. Two global transcriptional regulators, MgrA and NorG, are known to have direct regulatory roles in the expression of various of these pumps. The work described below has focused on i) defining the regulatory mechanisms that control pump expression (including the complex interactions of various regulators), ii) determination of the role of pump expression in the adaptation of S. aureus to survival in an abscess, its most common cause of infection, iii) determination of the environmental signals that trigger pump expression, and iv) defining the natural substrates of these generally broad-spectrum pumps, for which antimicrobials may be incidental substrates.