摘要

金黄色葡萄球菌在现代抗生素时代的进化已经由不同的菌株出现事件描述，其中许多包括获得抗生素抗性。耐甲氧西林金黄色葡萄球菌（MRSA）在医疗和社区环境中的相对高负担是全球主要关心的问题。万古霉素，一种抑制细胞壁生物合成的糖肽类抗生素，仍然是治疗严重MRSA感染的首选药物。在20世纪90年代发现了对万古霉素有抗药性的金黄色葡萄球菌，被称为万古霉素中度耐药金黄色葡萄球菌（VISA）（MIC =4-8μg/ mL）。 VISA中抗性的分子基础是多基因的并涉及编码主要参与细胞包膜生物合成的分子的基因的逐步突变。对万古霉素（MIC≥16μg/ mL）完全耐药的金黄色葡萄球菌分离株被称为万古霉素耐药金黄色葡萄球菌（VRSA） - 它们于2002年首次在美国报道。VRSA的耐药性由vanA基因和操纵子赋予，它存在于质粒上。虽然治疗VRSA感染具有挑战性，但迄今为止人类VRSA感染的总数量有限（美国为14例）。相比之下，VISA的负担相对较高，并且阻力的分子机制不太明确。 VISA与持续感染，万古霉素治疗失败和不良临床结果有关。在这里，我们简要回顾在理解获得金黄色葡萄球菌抗生素耐药性方面取得的进展，重点强调万古霉素耐药性的分子机制。

The evolution of Staphylococcus aureus during the modern antibiotic era has been delineated by distinct strain emergence events, many of which include acquisition of antibiotic resistance. The relative high burden of methicillin-resistant S. aureus (MRSA) in healthcare and community settings is a major concern worldwide. Vancomycin, a glycopeptide antibiotic that inhibits cell wall biosynthesis, remains a drug of choice for treatment of severe MRSA infections. S. aureus strains exhibiting increased resistance to vancomycin, known as vancomycin intermediate-resistant S. aureus (VISA) (MIC = 4-8 µg/mL), were discovered in the 1990s. The molecular basis of resistance in VISA is polygenic and involves stepwise mutations in genes encoding molecules predominantly involved in cell envelope biosynthesis. S. aureusisolates with complete resistance to vancomycin (MIC ≥ 16 µg/mL) are termed vancomycin-resistant S. aureus (VRSA)—they were first reported in the U.S. in 2002. Resistance in VRSA is conferred by thevanA gene and operon, which is present on a plasmid. Although treatment of VRSA infections is challenging, the total number of human VRSA infections to date is limited (14 in the U.S.). By comparison, the burden of VISA is relatively high and the molecular mechanisms of resistance are less well-defined. VISA are associated with persistent infections, vancomycin treatment failure, and poor clinical outcomes. Here, we review in brief progress made toward understanding the acquisition of antibiotic resistance in S. aureus, with an emphasis on the molecular mechanisms underlying vancomycin resistance.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482303/