title: The mecA homolog mecC confers resistance against β-lactams in Staphylococcus aureus irrespective of the genetic strain background.
abstract: In staphylococci, methicillin resistance is mediated by mecA-encoded penicillin-binding protein 2a (PBP2a), which has a low affinity for beta-lactams. Recently, a novel PBP2a homolog was described as being encoded by mecC, which shares only 70% similarity to mecA. To prove that mecC is the genetic determinant that confers methicillin resistance in Staphylococcus aureus, a mecC knockout strain was generated. The S. aureus ΔmecC strain showed considerably reduced oxacillin and cefoxitin MICs (0.25 and 4 μg/ml, respectively) compared to those of the corresponding wild-type methicillin-resistant S. aureus (MRSA) strain (8 and 16 μg/ml, respectively). Complementing the mutant in trans with wild-type mecC restored the resistance to oxacillin and cefoxitin. By expressing mecC and mecA in different S. aureus clonal lineages, we found that mecC mediates resistance irrespective of the genetic strain background, yielding oxacillin and cefoxitin MIC values comparable to those with mecA. In addition, we showed that mecC expression is inducible by oxacillin, which supports the assumption that a functional beta-lactam-dependent regulatory system is active in MRSA strains possessing staphylococcal cassette chromosome mec (SCCmec) type XI. In summary, we showed that mecC is inducible by oxacillin and mediates beta-lactam resistance in SCCmec type XI-carrying strains as well as in different S. aureus genetic backgrounds. Furthermore, our results could explain the comparatively low MICs for clinical mecC-harboring S. aureus isolates.
authors.affiliation: University Hospital Münster, Institute of Medical Microbiology, Münster, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Ballhausen
authors.affiliation: University Hospital Münster, Institute of Medical Microbiology, Münster, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Kriegeskorte
authors.affiliation: University Hospital Münster, Institute of Medical Microbiology, Münster, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Schleimer
authors.affiliation: University Hospital Münster, Institute of Medical Microbiology, Münster, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Peters
authors.affiliation: University Hospital Münster, Institute of Medical Microbiology, Münster, Germany kbecker@uni-muenster.de.
authors.forename: Karsten
authors.initials: K
authors.lastname: Becker
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D055786:Gene Knockout Techniques; D017930:Genes, Reporter / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D046915:Penicillin-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012329:RNA, Bacterial / Q000235:genetics; D013045:Species Specificity; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics*; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D046915:Penicillin-Binding Proteins; D012329:RNA, Bacterial; D047090:beta-Lactams; C487789:mecA protein, Staphylococcus aureus; D049452:Green Fluorescent Proteins
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