Two codependent routes lead to high-level MRSA

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ADEDEJI-OLULANA, Abimbola Feyisara, WACNIK, Katarzyna, LAFAGE, Lucia, PASQUINA-LEMONCHE, Laia, TINAJERO-TREJO, Mariana, SUTTON, Joshua A.F., BILYK, Bohdan, IRVING, Sophie E., PORTMAN ROSS, Callum J., 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. and FOSTER, Simon J. (2024). Two codependent routes lead to high-level MRSA. Science, 386 (6721), 573-580. [Article]

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34760:822474

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34760:822474

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Abstract

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.

More Information

Official URL:

https://www.science.org/doi/10.1126/science.adn136...

Additional Information:

The date of acceptance was sourced from White Rose repository

Uncontrolled Keywords:

Cell Wall; Penicillin-Binding Proteins; Peptidoglycan; Bacterial Proteins; Anti-Bacterial Agents; Methicillin Resistance; Cell Division; Mutation; Methicillin-Resistant Staphylococcus aureus; Anti-Bacterial Agents; Bacterial Proteins; Cell Division; Cell Wall; Methicillin-Resistant Staphylococcus aureus; Mutation; Penicillin-Binding Proteins; Peptidoglycan; Methicillin Resistance; General Science & Technology

Page Range:

573-580

Event Location:

United States

Identifiers

Identification Number:

10.1126/science.adn1369

ORCID for David S Owen: