Spontaneous mutation accompanying decreased growth rate and cell wall thickening confers vancomycin resistance in the subpopulation of heterogeneously vancomycim-resistaut strain Mu3.

Abstract

Objective : Heterogeneous vancomycin-resistant Staphylococcus aureus (hetero-VRSA) may cause vancomycin refractory infection due to its frequent generation of vancomycin-resistant cell subpopulations. We study whether a mutant having the same phenotypic properties as the clinical VRSA strains is generated within the resistant cell subpopulation of hetero-VRSA strain. Materials : Hetero-VRSA strain Mu3 was used. Methods : By using the fluctuation test of Luria and Delbrük we tested whether vancomycin-resistant mutants were generated spontaneously. Results : Vancomycin-resistant mutants occurred spontaneously at high frequencies of 2.5-4.9 × 10^-6 per cell division, and the mutants exhibited the characteristic phenotype of the vancomycin-resistant S.aureus clinical strains, i.e. thickened cell wall and reduced growth rate. Conclusions : This study implies that low-level vancomycin resistance may emerge at high frequency in the bodies of patients infected with hetero-VRSA strain.