The mecA Homolog mecC Confers Resistance against β-Lactams in Staphylococcus aureus Irrespective of the Genetic Strain Background

被引:61
作者
Ballhausen, Britta [1 ]
Kriegeskorte, Andre [1 ]
Schleimer, Nina [1 ]
Peters, Georg [1 ]
Becker, Karsten [1 ]
机构
[1] Univ Hosp Munster, Inst Med Microbiol, Munster, Germany
关键词
CASSETTE CHROMOSOME MEC; METHICILLIN RESISTANCE; MOLECULAR-CLONING; BINDING; EXPRESSION; VARIANT; MRSA; 2A; ANTIBIOTICS; MUTATIONS;
D O I
10.1128/AAC.02731-13
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 mecC strain showed considerably reduced oxacillin and cefoxitin MICs (0.25 and 4 mu g/ ml, respectively) compared to those of the corresponding wild-type methicillin-resistant S. aureus (MRSA) strain (8 and 16 mu g/ 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.
引用
收藏
页码:3791 / 3798
页数:8
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