ThemecAHomologmecCConfers Resistance against β-Lactams in Staphylococcus aureus Irrespective of the Genetic Strain Background

Abstract

ABSTRACTIn staphylococci, methicillin resistance is mediated bymecA-encoded penicillin-binding protein 2a (PBP2a), which has a low affinity for beta-lactams. Recently, a novel PBP2a homolog was described as being encoded bymecC, which shares only 70% similarity tomecA. To prove thatmecCis the genetic determinant that confers methicillin resistance inStaphylococcus aureus, amecCknockout strain was generated. TheS. aureusΔmecCstrain showed considerably reduced oxacillin and cefoxitin MICs (0.25 and 4 μg/ml, respectively) compared to those of the corresponding wild-type methicillin-resistantS. aureus(MRSA) strain (8 and 16 μg/ml, respectively). Complementing the mutant intranswith wild-typemecCrestored the resistance to oxacillin and cefoxitin. By expressingmecCandmecAin differentS. aureusclonal lineages, we found thatmecCmediates resistance irrespective of the genetic strain background, yielding oxacillin and cefoxitin MIC values comparable to those withmecA. In addition, we showed thatmecCexpression is inducible by oxacillin, which supports the assumption that a functional beta-lactam-dependent regulatory system is active in MRSA strains possessing staphylococcal cassette chromosomemec(SCCmec) type XI. In summary, we showed thatmecCis inducible by oxacillin and mediates beta-lactam resistance in SCCmectype XI-carrying strains as well as in differentS. aureusgenetic backgrounds. Furthermore, our results could explain the comparatively low MICs for clinicalmecC-harboringS. aureusisolates.