Multidrug resistance in Staphylococcus aureus due to overexpression of a novel multidrug and toxin extrusion (MATE) transport protein
Multidrug resistance in Staphylococcus aureus due to overexpression of a novel multidrug and toxin extrusion (MATE) transport protein
复制标题
DOI：
10.1128/aac.49.5.1857-1864.2005
复制
发表时间：
2005-05-01
影响因子：
4.9
通讯作者：
Seo, SM
中科院分区：
文献类型：
--
作者：
Kaatz, GW;McAleese, F;Seo, SM
外排是细菌多药耐药的重要机制。多药和毒素外排（MATE）家族是最近描述的MDR外排蛋白组，以前在金黄色葡萄球菌中没有发现。两个独立导出的S。使用微阵列技术研究了具有流出相关MDR表型的金黄色葡萄球菌突变体，并且在两者中观察到编码与MATE家族蛋白同源的蛋白的开放阅读框（ORF; mepA）的显著过表达。有伴随过度表达的ORF在接近mepA（类似于100 bp）编码的MarR型调节器（mepR，上游的mepA）和未知功能的蛋白质（mepB，下游）。mepA被过表达或破坏的实验表明，编码的蛋白质具有广泛的底物谱，包括几种单价和二价杀生物剂和氟喹诺酮类抗微生物剂诺氟沙星和环丙沙星。MepB的功能尚不清楚，它与MepA赋予的MDR表型无关。MepR过表达逆转MDR表型的两个突变体通过抑制mepA转录。所有三个ORF优先转录为一个单一的mepRAB单位，这表明这三个基因形成一个操纵子。
Efflux is an important mechanism of multidrug resistance (MDR) in bacteria. The multidrug and toxin extrusion (MATE) family is the most recently described group of MDR efflux proteins, none of which have previously been identified in Staphylococcus aureus. Two independently derived S. aureus mutants having efflux-related MDR phenotypes were studied using microarray technology and a marked overexpression of an open reading frame (ORF; mepA) encoding a protein homologous with MATE family proteins was observed in both. There was concomitant overexpression of ORFs in close proximity to mepA (similar to 100 bp) encoding a MarR-type regulator (mepR, upstream of mepA) and a protein of unknown function (mepB, downstream). Experiments in which mepA was overexpressed or disrupted revealed that the encoded protein has a broad substrate profile that includes several monovalent and divalent biocides and the fluoroquinolone antimicrobial agents norfloxacin and ciprofloxacin. The function of MepB is obscure, it does not contribute to the MDR phenotype conferred by MepA. MepR overexpression reversed the MDR phenotypes of both mutants by repressing mepA transcription. All three ORFs are preferentially transcribed as a single mepRAB unit, suggesting that the three genes form an operon.