Ba, X., Harrison, E., Lovering, A., Gleadall, N., Zadoks, R. , Parkhill, J., Peacock, S., Holden, M., Paterson, G. K. and Holmes, M. (2015) Old drugs to treat resistant bugs: methicillin-resistant staphylococcus aureus Isolates with mecCAre susceptible to a combination of penicillin and clavulanic acid. Antimicrobial Agents and Chemotherapy, 59(12), pp. 7396-7404. (doi: 10.1128/aac.01469-15) (PMID:26392513)
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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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Zadoks, Professor Ruth |
| Authors: | Ba, X., Harrison, E., Lovering, A., Gleadall, N., Zadoks, R., Parkhill, J., Peacock, S., Holden, M., Paterson, G. K., and Holmes, M. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine |
| Journal Name: | Antimicrobial Agents and Chemotherapy |
| Publisher: | American Society for Microbiology |
| ISSN: | 0066-4804 |
| ISSN (Online): | 1098-6596 |
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