摘要
      在这篇综述中，我们讨论了细菌剂金黄色葡萄球菌和肠球菌对两种优先级抗生素 - 氟喹诺酮类和糖肽类的抗性机制。两类成员都与这些细菌细胞中的许多成分相互作用，因此也考虑了细胞靶点。氟喹诺酮耐药机制包括外排泵（MepA，NorA，NorB，NorC，MdeA，LmrS或SdrM在金黄色葡萄球菌中和EfmA或EfrAB在肠球菌中）用于从细菌细胞的细胞内环境中去除氟喹诺酮和/或保护促旋酶和Qnr样蛋白在粪肠球菌中的拓扑异构酶IV靶位点。外排系统的表达受GntR样（金黄色葡萄球菌NorG），MarR样（MgrA，MepR）调节剂或双组分信号转导系统（TCS）（金黄色葡萄球菌ArlSR）调节。对糖肽抗生素替考拉宁的抗性通过金葡菌中的TcaR调节剂调节的外排发生。通过修饰细胞壁肽聚糖中的D-Ala-D-Ala靶标并去除高亲和力前体，或通过细胞壁增厚的靶保护，发生对万古霉素的抗性。在这六种Van阻力类型（VanA-E，VanG）中，VanA阻力类型在本评价中被考虑，包括VanSR TCS的规定。我们描述了生物物理学方法的最近应用，例如分析超速离心和圆二色光谱的流体动力学技术以鉴定激活Van抗性基因表达的VanS受体的可能分子效应物;两种方法均表明万古霉素与VanS相互作用，表明万古霉素本身（或具有辅助因子的万古霉素）可能是万古霉素耐药性的效应物。我们提出，分别涉及氟喹诺酮和糖肽抗性的16和19种蛋白质或蛋白质复合物以及触发和调节各种可能的抗性机制的细菌感应机制的复杂性，我们提出这些抗微生物药物抗性机制可能被认为是复杂的“纳米机器”这推动了抗生素环境中细菌细胞的存活。

      In this review, we discuss mechanisms of resistance identified in bacterial agents Staphylococcus aureus and the enterococci towards two priority classes of antibiotics-the fluoroquinolones and the glycopeptides. Members of both classes interact with a number of components in the cells of these bacteria, so the cellular targets are also considered. Fluoroquinolone resistance mechanisms include efflux pumps (MepA, NorA, NorB, NorC, MdeA, LmrS or SdrM in S. aureus and EfmA or EfrAB in the enterococci) for removal of fluoroquinolone from the intracellular environment of bacterial cells and/or protection of the gyrase and topoisomerase IV target sites in Enterococcus faecalis by Qnr-like proteins. Expression of efflux systems is regulated by GntR-like (S. aureus NorG), MarR-like (MgrA, MepR) regulators or a two-component signal transduction system (TCS) (S. aureus ArlSR). Resistance to the glycopeptide antibiotic teicoplanin occurs via efflux regulated by the TcaR regulator in S. aureus. Resistance to vancomycin occurs through modification of the D-Ala-D-Ala target in the cell wall peptidoglycan and removal of high affinity precursors, or by target protection via cell wall thickening. Of the six Van resistance types (VanA-E, VanG), the VanA resistance type is considered in this review, including its regulation by the VanSR TCS. We describe the recent application of biophysical approaches such as the hydrodynamic technique of analytical ultracentrifugation and circular dichroism spectroscopy to identify the possible molecular effector of the VanS receptor that activates expression of the Van resistance genes; both approaches demonstrated that vancomycin interacts with VanS, suggesting that vancomycin itself (or vancomycin with an accessory factor) may be an effector of vancomycin resistance. With 16 and 19 proteins or protein complexes involved in fluoroquinolone and glycopeptide resistances, respectively, and the complexities of bacterial sensing mechanisms that trigger and regulate a wide variety of possibleresistance mechanisms, we propose that these antimicrobial resistance mechanisms might be considered complex 'nanomachines' that drive survival of bacterial cells in antibiotic environments.

https://www.ncbi.nlm.nih.gov/pubmed/29525835