School of Mathematical and Physical Sciences, University of Sheffield, Sheffield, UK.
School of Biosciences, University of Sheffield, Sheffield, UK.
Science. 2024 Nov;386(6721):573-580. doi: 10.1126/science.adn1369. Epub 2024 Oct 31.
Methicillin-resistant (MRSA), in which acquisition of [which encodes the cell wall peptidoglycan biosynthesis component penicillin-binding protein 2a (PBP2a)] confers resistance to β-lactam antibiotics, is of major clinical concern. We show that, in the presence of antibiotics, MRSA adopts an alternative mode of cell division and shows an altered peptidoglycan architecture at the division septum. PBP2a can replace the transpeptidase activity of the endogenous and essential PBP2 but not that of PBP1, which is responsible for the distinctive native septal peptidoglycan architecture. Successful division without PBP1 activity requires the alternative division mode and is enabled by several possible chromosomal potentiator () mutations. MRSA resensitizing agents differentially interfere with the two codependent mechanisms required for high-level antibiotic resistance, which provides opportunities for new interventions.
耐甲氧西林金黄色葡萄球菌（MRSA），其中获取[其编码细胞壁肽聚糖生物合成成分青霉素结合蛋白 2a（PBP2a）]赋予对β-内酰胺抗生素的抗性，是主要的临床关注。我们表明，在抗生素存在的情况下，MRSA 采用替代的细胞分裂模式，并在分裂隔膜处显示出改变的肽聚糖结构。PBP2a 可以替代内源性和必需的 PBP2 的转肽酶活性，但不能替代负责独特的天然隔膜肽聚糖结构的 PBP1。没有 PBP1 活性的成功分裂需要替代的分裂模式，并且可以通过几种可能的染色体增强子（）突变来实现。MRSA 再敏化剂差异地干扰两种相互依赖的机制，这些机制是高水平抗生素抗性所必需的，这为新的干预措施提供了机会。
