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Old drugs to treat resistant bugs: Methicillin-resistant Staphylococcus aureus isolates with mecC are susceptible to a combination of penicillin and clavulanic acid

Ba, Xiaoliang; Harrison, Ewan M.; Lovering, Andrew L.; Gleadall, Nicholas; Zadoks, Ruth; Parkhill, Julian; Peacock, Sharon J.; Holden, Matthew T. G.; Paterson, Gavin K.; Holmes, Mark A.

Authors

Xiaoliang Ba

Ewan M. Harrison

Andrew L. Lovering

Nicholas Gleadall

Ruth Zadoks

Julian Parkhill

Sharon J. Peacock

Matthew T. G. Holden

Gavin K. Paterson

Mark A. Holmes

Abstract

β-Lactam resistance in methicillin-resistant Staphylococcus aureus (MRSA) is mediated by the expression of an alternative penicillin-binding protein 2a (PBP2a) (encoded by mecA) with a low affinity for β-lactam antibiotics. Recently, a novel variant of mecA, known as mecC, was identified in MRSA isolates from both humans and animals. In this study, we demonstrate that mecC-encoded PBP2c does not mediate resistance to penicillin. Rather, broad-spectrum β-lactam resistance in MRSA strains carrying mecC (mecC-MRSA strains) is mediated by a combination of both PBP2c and the distinct β-lactamase encoded by the blaZ gene of strain LGA251 (blaZLGA251), which is part of mecC-encoding staphylococcal cassette chromosome mec (SCCmec) type XI. We further demonstrate that mecC-MRSA strains are susceptible to the combination of penicillin and the β-lactam inhibitor clavulanic acid in vitro and that the same combination is effective in vivo for the treatment of experimental mecC-MRSA infection in wax moth larvae. Thus, we demonstrate how the distinct biological differences between mecA- and mecC-encoded PBP2a and PBP2c have the potential to be exploited as a novel approach for the treatment of mecC-MRSA infections.

Journal Article Type Article
Publication Date Dec 1, 2015
Journal Antimicrobial agents and chemotherapy
Print ISSN 0066-4804
Electronic ISSN 1098-6596
Publisher American Society for Microbiology
Peer Reviewed Peer Reviewed
Volume 59
Issue 12
Pages 7396-7404
Institution Citation Ba, X., Harrison, E. M., Lovering, A. L., Gleadall, N., Zadoks, R., Parkhill, J., …Holmes, M. A. (2015). Old drugs to treat resistant bugs: Methicillin-resistant Staphylococcus aureus isolates with mecC are susceptible to a combination of penicillin and clavulanic acid. Antimicrobial agents and chemotherapy, 59(12), (7396-7404). doi:10.1128/AAC.01469-15. ISSN 0066-4804
DOI https://doi.org/10.1128/AAC.01469-15
Keywords β-lactams, MRSA, mecC
Publisher URL http://aac.asm.org/content/59/12/7396.abstract?sid=c132dcf3-0c8a-419b-b3c9-a00b500bff8f
Copyright Statement © 2015, American Society for Microbiology. All Rights Reserved.
Additional Information Copy of article first published in: Antimicrobial agents and chemotherapy, 2015, v.59, issue 12

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Copyright Statement
© 2015, American Society for Microbiology. All Rights Reserved.



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