Methicillin/oxacillin (Oxa) resistance in Staphylococcus aureus is primarily mediated by the acquired penicillin-binding protein (PBP2a) encoded by mecA. PBP2a acts together with native PBP2 to mediate oxacillin resistance by contributing complementary transpeptidase and transglycosylase activities, respectively. The VraS/VraR two-component regulatory system is inducible by cell-wall antimicrobials (beta-lactams, glycopeptides) and controls transcriptional induction of many cell-wall genes including pbp2 and itself. We investigated the role of VraS/VraR in the phenotypic expression of oxacillin resistance by inactivating vraS in community-acquired MRSA clinical isolates that lack functional genes encoding the mecA regulatory sequences mecI and mecR1. Inactivation of vraS abrogated oxacillin resistance, and complementation with the vraS operon restored the resistance phenotype. mecA transcription increased in the vraS mutants; however, PBP2a abundance was similar to that of the wild type. Although pbp2 transcription decreased in the vraS mutants, overexpression of the pbp2 operon did not restore resistance. These data demonstrate that although expressions of mecA and pbp2 are required for oxacillin resistance, they are not sufficient. Therefore, the vraS/vraR regulatory system plays a crucial role in allowing MRSA to respond to beta-lactams by regulation of a gene target other than the known effectors of methicillin resistance.

译文

金黄色葡萄球菌对甲氧西林/奥沙西林(Oxa)的耐药性主要由mecA编码的获得性青霉素结合蛋白(PBP2a)介导。 PBP2a与天然PBP2共同发挥作用,通过分别贡献互补的转肽酶和转糖基酶活性来介导奥沙西林抗性。 VraS / VraR两组分调节系统可通过细胞壁抗微生物剂(β-内酰胺,糖肽)诱导,并控制包括pbp2及其本身在内的许多细胞壁基因的转录诱导。我们通过灭活社区获得的MRSA临床分离株中的vraS而失活,研究了VraS / VraR在奥沙西林耐药性表型表达中的作用,该分离株缺乏编码mecA调控序列mecI和mecR1的功能基因。 vraS的失活消除了奥沙西林的耐药性,与vraS操纵子的互补恢复了耐药性表型。在vraS突变体中,mecA转录增加;但是,PBP2a的丰度与野生型相似。尽管在vraS突变体中pbp2转录降低,但是pbp2操纵子的过表达不能恢复抗性。这些数据表明,尽管抗mecA和pbp2的表达是奥沙西林耐药性所必需的,但它们还不够。因此,vraS / vraR调节系统在允许MRSA通过调节除已知的甲氧西林抗性效应子以外的基因靶标而对β-内酰胺作出响应中起着至关重要的作用。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录