Antimicrob Agents Chemother2001 Jul;45(7):1955-63
Department of Bacteriology, Juntendo University, Tokyo 113-8421, Japan.
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-IS431R (or IS431mec), designated
the class A mecA gene complex. In contrast, in S. haemolyticus, mecA was
bracketed by two copies of IS431, forming the structure IS431L-mecA-IS431R.
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, IS431L
was located to the left of an intact mecI gene, forming the structure
IS431L-class A mecA-gene complex. In other S. haemolyticus strains, IS431L
was associated with the deletion of mecI and mecR1, forming the structure
IS431L-DeltamecR1-mecA-IS431mec, 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 IS431L-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 IS431-mediated mecI
gene deletion causes the expression of methicillin resistance through the
derepression of mecA gene transcription.