Genetic Organization of the Chromosome Region Surrounding mecA in Clinical Staphylococcal Strains: Role of IS 431 -Mediated mecI Deletion in Expression of Resistance in mecA -Carrying, Low-Level Methicillin- Resistant Staphylococcus haemolyticus

Abstract

We report on the structural diversity of mecA gene complexes carried by 38 methicillin-resistant Staphylococcus aureus and 91 methicillin-resistant coagulase-negative Staphylococcus strains of seven different species with a special reference to its correlation with phenotypic expression of methicillin resistance. The most prevalent and widely disseminated mec complex had the structure mecI-mecR1-mecA -IS 431R (or IS 431mec ), designated the class A mecA gene complex. In contrast, in S. haemolyticus, mecA was bracketed by two copies of IS 431 , forming the structure IS 431L-mecA -IS 431R . Of the 38 S. haemolyticus strains, 5 had low-level methicillin resistance (MIC, 1 to 4 mg/liter) and characteristic heterogeneous methicillin resistance as judged by population analysis. In these five strains, IS 431L was located to the left of an intact mecI gene, forming the structure IS 431L -class A mecA -gene complex. In other S. haemolyticus strains, IS 431L was associated with the deletion of mecI and mecR1 , forming the structure IS 431L -Δ mecR1-mecA -IS 431mec , designated the class C mecA gene complex. Mutants with the class C mecA gene complex were obtained in vitro by selecting strain SH621, containing the IS 431L -class A mecA gene complex with low concentrations of methicillin (1 and 3 mg/liter). The mutants had intermediate level of methicillin resistance (MIC, 16 to 64 mg/liter). The mecA gene transcription was shown to be derepressed in a representative mutant strain, SH621-37. Our study indicated that the mecI -encoded repressor function is responsible for the low-level methicillin resistance of some S. haemolyticus clinical strains and that the IS 431 -mediated mecI gene deletion causes the expression of methicillin resistance through the derepression of mecA gene transcription.