MecA/C Resistance Markers
The mecA and mecC genes are genetic resistance markers that encode alternative penicillin-binding proteins (PBP2a and PBP2c) with low affinity for β-lactam antibiotics, conferring methicillin resistance in Staphylococcus aureus and other staphylococci. 1, 2
Molecular Basis of Resistance
The mecA gene encodes PBP2a, which allows bacterial cell-wall biosynthesis to continue even in the presence of β-lactam antibiotics that would normally inhibit this process. 1 This resistance mechanism is carried on a mobile genetic element called the staphylococcal cassette chromosome mec (SCCmec), which contains both the mec gene complex and the ccr gene complex with site-specific recombinase genes. 1
The mecC gene is a more recently discovered homolog that shares only 70% similarity with mecA but confers the same methicillin resistance phenotype. 3 The mecC-encoded protein PBP2c mediates β-lactam resistance irrespective of the genetic strain background, yielding oxacillin and cefoxitin MIC values comparable to mecA-carrying strains. 3
Clinical Significance as Diagnostic Markers
The Clinical and Laboratory Standards Institute designates molecular detection of mecA or mecC as the gold-standard method for defining methicillin resistance when Staphylococcus aureus is also identified. 2 This represents a critical shift from phenotypic to genotypic diagnosis.
Key diagnostic advantages:
- PCR results are available in 4-6 hours compared to 48-72 hours for conventional culture-based methods. 2
- Simultaneous detection of S. aureus DNA and mecA/mecC by PCR is sufficient to diagnose MRSA and should direct immediate antimicrobial therapy without awaiting phenotypic susceptibility results. 2
- Both mecA and mecC must be included in PCR panels to avoid false-negative results, as some MRSA strains harbor the mecC homolog instead of mecA. 2
Surveillance and Detection Methods
Surveillance can target these resistance markers through three approaches: direct gene detection (mecA/mecC via PCR), detection of the encoded protein products (PBP2a via monoclonal antibodies), or identification of characteristic resistance phenotypes. 1
The mecA gene can be detected using PCR-based methods, with newer nucleic acid lateral flow immunoassay (NALFIA) technology allowing differentiation between mecA and mecC by visualizing the two alleles at different positions on test stripes. 4
SCCmec Classification and Epidemiology
The SCCmec elements have been classified into eight types (I-VIII) based on the structure and combination of mec and ccr gene complexes. 1 This classification helps distinguish hospital-acquired MRSA (HA-MRSA) from community-acquired MRSA (CA-MRSA):
- HA-MRSA strains typically carry SCCmec types I, II, III, VI, and VIII, which may contain additional resistance genes such as ermA (erythromycin), aadD (tobramycin), and tetK (tetracycline). 1
- CA-MRSA strains typically carry SCCmec type IV, with some carrying types V and VII, generally without other resistance genes. 1
Important Clinical Caveats
In the rare (<1%) scenario of genotypic-phenotypic discordance (mecA-positive but phenotypically susceptible), CLSI advises treating the isolate as methicillin-resistant. 2 This conservative approach prioritizes patient safety and prevents treatment failure.
MecC-MRSA strains have distinct biological properties: they show comparatively lower MICs for oxacillin and cefoxitin than mecA-MRSA strains, and interestingly, mecC-MRSA strains may be susceptible to the combination of penicillin and clavulanic acid because PBP2c alone does not mediate full penicillin resistance. 3, 5 However, this should not alter standard MRSA treatment protocols in clinical practice.
Immediate Treatment Implications
When PCR identifies both S. aureus and mecA or mecC, treatment should commence immediately as MRSA with the following regimens: 2
- Vancomycin 15-20 mg/kg IV every 8-12 hours
- Daptomycin 10 mg/kg IV once daily
- Linezolid 600 mg orally or IV twice daily
For mecA/mecC-negative S. aureus (MSSA), use β-lactam agents such as nafcillin, oxacillin, or cefazolin, allowing de-escalation from empiric vancomycin therapy. 2
Each additional day of delayed culture clearance is associated with increased attributable mortality, making rapid mecA/mecC detection clinically impactful for patient outcomes. 2