We investigated changes in regulatory genes, vraS and graR, during development of vancomycin non-susceptibility in a patient with methicillin-resistant Staphylococcus aureus who failed therapy and following in-vitro vancomycin exposure and a subsequent drug-free growth period. Minimum Inhibitory Concentration (MICs) were determined and genes sequenced at each stage. After 30days of vancomycin exposure, the strain attained maximum MIC (20mg/L) and was resistant to all antibiotics. Reversion to vancomycin susceptibility occurred 21days after removal. We observed mutations in vraS and graR during non-susceptibly development and novel stop codons in the reverted strain. Mutations in graR appear important for development of intermediate susceptibility to vancomycin. The results suggest that monitoring of vancomycin therapy could allow earlier change to appropriate agents.
- Methicillin-resistant Staphylococcus aureus
- Treatment failure
- Two component regulatory systems
- Vancomycin intermediately-susceptible
ASJC Scopus subject areas
- Microbiology (medical)
- Infectious Diseases