Tracking the Evolutionary Origin of the Methicillin Resistance Gene: Cloning and Sequencing of a Homologue ofmecAfrom a Methicillin Susceptible Strain ofStaphylococcus sciuri

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Abstract
The gene mecA, a central genetic determinant of methicillin resistance in Staphylococcus aureus and coagulase-negative staphylococci of human origin, has an unknown extra species origin in these human pathogens. After screening isolates representing over 15 different species within the genus Staphylococcus we could identify only one—S. sciuri—in which each of over 150 independent isolates showed positive hybridization with a mec A-specific DNA probe isolated from a methicillin-resistant strain of S. aureus, (MRSA). Yet, the majority of these isolates showed no resistance to penicillin or methicillin. The mecA gene homologue was cloned and sequenced from a S. sciuri strain and the sequence of mecA was compared to that of the mecA of prototype strains of methicillin resistant S. aureus and S. epidermidis. Similarly to mecA of MRSA, the mecA homologue of S. sciuri was composed of a putative transglycosylase and a transpeptidase domain the latter showing all the conserved motifs typical of the active sites of the penicillin binding domain of transpeptidases. Overall similarity between the deduced amino acid sequences of mecA of MRSA and the mecA homologue of S. sciuri was 88%. On the other hand, comparison of the transpeptidase domain of the S. sciuri mecA to the corresponding domain alone of the MRSA mecA showed a similarity of 96% and an identity of 91%, while comparison of the putative transglycosylase domains of the two bacteria showed only a 80% similarity and 68% identity of amino acid sequences. Our data suggests that mecA of methicillin-resistant strains of staphylococci pathogenic to Man originated within the genus of Staphylococcus from an evolutionary relative of the mecA homologue that we have identified in S. sciuri and which may perform a normal physiological function in this bacterium unrelated to β-lactam resistance.