Two codependent routes lead to high-level MRSA.

Autor: Adedeji-Olulana AF; School of Mathematical and Physical Sciences, University of Sheffield, Sheffield, UK., Wacnik K; School of Biosciences, University of Sheffield, Sheffield, UK.; The Florey Institute, University of Sheffield, Sheffield, UK., Lafage L; School of Biosciences, University of Sheffield, Sheffield, UK.; The Florey Institute, University of Sheffield, Sheffield, UK., Pasquina-Lemonche L; School of Mathematical and Physical Sciences, University of Sheffield, Sheffield, UK.; The Florey Institute, University of Sheffield, Sheffield, UK., Tinajero-Trejo M; School of Biosciences, University of Sheffield, Sheffield, UK.; The Florey Institute, University of Sheffield, Sheffield, UK., Sutton JAF; School of Biosciences, University of Sheffield, Sheffield, UK.; The Florey Institute, University of Sheffield, Sheffield, UK., Bilyk B; School of Biosciences, University of Sheffield, Sheffield, UK.; The Florey Institute, University of Sheffield, Sheffield, UK., Irving SE; School of Biosciences, University of Sheffield, Sheffield, UK.; The Florey Institute, University of Sheffield, Sheffield, UK., Portman Ross CJ; School of Biosciences, University of Sheffield, Sheffield, UK.; The Florey Institute, University of Sheffield, Sheffield, UK., Meacock OJ; School of Mathematical and Physical Sciences, University of Sheffield, Sheffield, UK., Randerson SA; School of Mathematical and Physical Sciences, University of Sheffield, Sheffield, UK., Beattie E; School of Mathematical and Physical Sciences, University of Sheffield, Sheffield, UK., Owen DS; School of Biosciences, University of Sheffield, Sheffield, UK., Florence J; School of Biosciences, University of Sheffield, Sheffield, UK.; The Florey Institute, University of Sheffield, Sheffield, UK., Durham WM; School of Mathematical and Physical Sciences, University of Sheffield, Sheffield, UK., Hornby DP; School of Biosciences, University of Sheffield, Sheffield, UK.; The Florey Institute, University of Sheffield, Sheffield, UK., Corrigan RM; School of Biosciences, University of Sheffield, Sheffield, UK.; The Florey Institute, University of Sheffield, Sheffield, UK.; School of Medicine, University College Dublin, Dublin, Ireland., Green J; School of Biosciences, University of Sheffield, Sheffield, UK.; The Florey Institute, University of Sheffield, Sheffield, UK., Hobbs JK; School of Mathematical and Physical Sciences, University of Sheffield, Sheffield, UK., Foster SJ; School of Biosciences, University of Sheffield, Sheffield, UK.; The Florey Institute, University of Sheffield, Sheffield, UK.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2024 Nov; Vol. 386 (6721), pp. 573-580. Date of Electronic Publication: 2024 Oct 31.
DOI: 10.1126/science.adn1369
Abstrakt: 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 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 ( pot ) mutations. MRSA resensitizing agents differentially interfere with the two codependent mechanisms required for high-level antibiotic resistance, which provides opportunities for new interventions.
Databáze: MEDLINE