Genetic organization of the chromosome region surrounding mecA in clinical staphylococcal strains: role of IS431-mediated mecI deletion in expression of 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 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.
Katayama
Y
Y
Department of Bacteriology, Faculty of Medicine, Juntendo University, Tokyo, Japan.
Ito
T
T
Hiramatsu
K
K
D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002876:Chromosomes, Bacterial; D004251:DNA Transposable Elements / Q000235:genetics; D017353:Gene Deletion; D016680:Genome, Bacterial; D006602:Hexosyltransferases; D006801:Humans; D016106:Methicillin Resistance / Q000235:genetics*; D002267:Muramoylpentapeptide Carboxypeptidase / Q000235:genetics* / Q000378:metabolism; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D012097:Repressor Proteins / Q000235:genetics*; D013210:Staphylococcus / Q000235:genetics*; D014158:Transcription, Genetic
D001426:Bacterial Proteins; D002352:Carrier Proteins; D004251:DNA Transposable Elements; C101640:MecI protein, Staphylococcus; D046915:Penicillin-Binding Proteins; D012097:Repressor Proteins; C083616:mecA protein, Bacillus subtilis; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase