Two codependent routes lead to high-level MRSA

• 成果类型: Article
• 署名作者: Adedeji-Olulana, Abimbola Feyisara; Wacnik, Katarzyna; Lafage, Lucia; Pasquina-Lemonche, Laia; Tinajero-Trejo, Mariana; Sutton, Joshua A. F.; Bilyk, Bohdan; Irving, Sophie E.; Ross, Callum J. Portman; Meacock, Oliver J.; Randerson, Sam A.; Beattie, Ewan; Owen, David S.; Florence, James; Durham, William M.; Hornby, David P.; Corrigan, Rebecca M.; Green, Jeffrey; Hobbs, Jamie K.; Foster, Simon J.
• 署名单位: University of Sheffield; University of Sheffield; University of Sheffield; University College Dublin; Sheffield Hallam University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-12621
• DOI: 10.1126/science.adn1369
• 发表日期: 2024-11-01
• 关键词: beta-lactam-resistance; cell-wall; methicillin resistance; virulence; strains; susceptibility; transmission; expression; EVOLUTION; division

摘要

Methicillin-resistant Staphylococcus aureus (MRSA), in which acquisition of mecA [which encodes the cell wall peptidoglycan biosynthesis component penicillin-binding protein 2a (PBP2a)] confers resistance to beta-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 (pot) mutations. MRSA resensitizing agents differentially interfere with the two codependent mechanisms required for high-level antibiotic resistance, which provides opportunities for new interventions.