Old Drugs To Treat Resistant Bugs: Methicillin-Resistant Staphylococcus aureus Isolates with mecC Are Susceptible to a Combination of Penicillin and Clavulanic Acid.

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.

• 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
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 59 Issue 12 Pg. 7396-404 (Dec 2015) ISSN: 1098-6596 [Electronic] United States
• PMID: 26392513 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Chemical References

• Bacterial Proteins
• Penicillin-Binding Proteins
• Penicillins
• beta-Lactamase Inhibitors
• mecA protein, Staphylococcus aureus
• Clavulanic Acid
• beta-Lactamases

Topics

• Animals
• Bacterial Proteins (genetics)
• Clavulanic Acid (pharmacology)
• Drug Interactions
• Drug Resistance, Bacterial (drug effects)
• Larva (drug effects, microbiology)
• Methicillin-Resistant Staphylococcus aureus (drug effects, genetics, isolation & purification)
• Microbial Sensitivity Tests
• Moths (drug effects, microbiology)
• Mutation
• Penicillin Resistance (drug effects, genetics)
• Penicillin-Binding Proteins (genetics)
• Penicillins (pharmacology)
• beta-Lactamase Inhibitors (pharmacology)
• beta-Lactamases (genetics)