Characterization of passage-selected vancomycin-resistant Staphylococcus aureus strains of diverse parental backgrounds

A series of 12 Staphylococcus aureus strains of various genetic backgrounds , methicillin resistance levels, and autolytic activities were subjected to selection for the glycopeptide-intermediate S. aureus (GISA) susceptibilit y phenotype on increasing concentrations of vancomycin, Six strains acquire d the phenotype rapidly, two did so slowly, and four failed to do so. The v ancomycin MICs for the GISA strains ranged from 4 to 16 mu g/ml, were stabl e to 20 nonselective passages, and expressed resistance homogeneously. Neit her ease of acquisition of the GISA phenotype nor the MIC attained correlat ed with methicillin resistance hetero- versus homogeneity or autolytic defi ciency or sufficiency, Oxacillin MICs were generally unchanged between pare nt and GISA strains, although the mec members of both isogenic methicillin- susceptible and methicillin-resistant pairs acquired the GISA phenotype mor e rapidly and to higher MICs than did their susceptible counterparts. Trans mission electron microscopy revealed that the GISA strains appeared normal in the absence of vancomycin but had thickened and diffuse cell walls when grown with vancomycin at one-half the MIG. Common features among GISAs were reduced doubling times, decreased lysostaphin susceptibilities, and reduce d whole-cell and zymographic autolytic activities in the absence of vancomy cin, This, with surface hydrophobicity differences, indicated that even in the absence of vancomycin the GISA cell walls differed from those of the pa rents. Autolytic activities were further reduced by the inclusion of vancom ycin in whole-cell and zymographic studies. The six Least vancomycin-suscep tible GISA strains exhibited an increased capacity to remove vancomycin fro m the medium versus their parent lines. This study suggests that while some elements of the GISA phenotype are strain specific, many are common to the phenotype although their expression is influenced by genetic background. G ISA strains with similar glycopeptide MICs may express individual component s of the phenotype to different extents.