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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

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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

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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.
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Original languageEnglish
Pages (from-to)7396-7404
Number of pages9
JournalAntimicrobial Agents and Chemotherapy
Volume59
Issue number12
Early online date21 Sep 2015
DOIs
StatePublished - Dec 2015

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