Affiliation:
1. Departments of Medicine
2. Microbiology/Immunology
3. Biostatistics, Medical College of Virginia at Virginia Commonwealth University, Richmond, Virginia
Abstract
ABSTRACT
Staphylococci that acquire the
mecA
gene are usually resistant to β-lactam antibiotics (methicillin or oxacillin resistance).
mecA
encodes a penicillin-binding protein (PBP 2a) that has a reduced affinity for β-lactams. In some isolates with methicillin or oxacillin resistance, only a small proportion (≤0.1%) of the population expresses resistance to ≥10 μg of oxacillin per ml (heterotypic resistance [HeR]), while in other isolates most of the population expresses resistance (homotypic resistance [HoR]). In the present study, growth of
Staphylococcus aureus
or
Staphylococcus epidermidis
strains with HeR in concentrations of oxacillin (0.3 to 0.7 μg/ml) that produced a fall or a lag in optical density converted the strains from the HeR to the HoR phenotype. The conversion from the HeR to the HoR phenotype appeared to be due to the selection of a highly resistant mutant population, as determined by fluctuation analysis and the failure of populations with HoR to revert to HeR after 60 generations of growth in antibiotic-free media. The frequencies of conversion were as high as 10
−3
to 10
−2
. Conversion to HoR required an intact
mecA
gene and an increase in the level of
mecA
transcription since no highly resistant subpopulation could be selected after growth in oxacillin when
mecA
transcription was constitutively repressed or when
mecA
had been inactivated. In addition, in both
S. epidermidis
and
S. aureus
the level of resistance to vancomycin, which also acts directly on the staphylococcal cell wall, was greater among convertants with HoR than their isogenic parents. The conversion of a population from HeR to HoR involves the selection of a mutation(s) that occurs at a high frequency and most likely requires abundant PBP 2a.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
50 articles.
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