Genetic organization of the chromosome region surrounding mecA in clinicalstaphylococcal strains: Role of IS431-mediated mecI deletion in expressionof resistance in mecA-carrying, low-level methicillin-resistant Staphylococcus haemolyticus

We report on the structural diversity of mecA gene complexes carried by 38 methicillin-resistant Staphylococcus aureus and 91 methicillin-resistant co agulase-negative Staphylococcus strains of seven different species with a s pecial reference to its correlation with phenotypic expression of methicill in resistance. The most prevalent and widely disseminated mec complex had t he structure mecI-mecR1-mecA-IS431R (or IS431mec), designated the class A m ecA gene complex. In contrast, in S. haemolyticus, mecA was bracketed by tw o copies of IS431, forming the structure IS431L-mecA-IS431R. Of the 38 S, h aemolyticus strains, 5 had low-level methicillin resistance (MIC, 1 to 4 mg /liter) and characteristic heterogeneous methicillin resistance as judged b y population analysis. In these five strains, IS431L was located to the lef t of an intact mecI gene, forming the structure IS431L-class A mecA-gene co mplex. In other S. haemolyticus strains, IS431L was associated with the del etion of mecI and mecR1, forming the structure IS431L-Delta mecR1-mecA-IS43 1mec, designated the class C mecA gene complex, Mutants with the class C me cA gene complex were obtained in vitro by selecting strain SH621, containin g the IS431L-class A mecA gene complex with low concentrations of methicill in (1 and 3 mg/liter). The mutants had intermediate level of methicillin re sistance (MIC, 16 to 64 mg/liter), The mecA gene transcription was shown to be derepressed in a representative mutant strain, SH621-37. Our study indi cated that the mecI-encoded repressor function is responsible for the low-l evel methicillin resistance of some S, haemolyticus clinical strains and th at the IS431-mediated mecI gene deletion causes the expression of methicill in resistance through the derepression of mecA gene transcription.