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Attenuated vancomycin bactericidal activity against Staphylococcus aureus hemB mutants expressing the
Brian T Tsuji1, Christof von Eiff, Pamela A Kelchlin
1School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, 331 Cooke Hall, Buffalo, NY 14260, USA. btsuji@buffalo.edu
Antimicrobial Agents and Chemotherapy
|February 21, 2008
Summary
Vancomycin was less effective against Staphylococcus aureus hemB mutants. This finding, showing reduced killing activity, was modeled using pharmacodynamics.
Area of Science:
- Microbiology
- Pharmacology
- Bacterial genetics
Background:
- Staphylococcus aureus is a common pathogen.
- Small-colony variants (SCVs) of S. aureus are associated with persistent infections.
- The hemB gene is crucial for heme biosynthesis in bacteria.
Purpose of the Study:
- To investigate the in vitro bactericidal activity of vancomycin against S. aureus hemB mutants.
- To compare vancomycin efficacy against hemB mutants and their parental strains.
- To model the pharmacodynamics of vancomycin killing.
Main Methods:
- In vitro susceptibility testing of vancomycin.
- Cultivation of S. aureus hemB mutants and parental strains.
- Pharmacodynamic modeling using a Hill-type equation.
Main Results:
- Vancomycin exhibited significantly reduced bactericidal activity against hemB mutants compared to parental strains.
- The killing effect of vancomycin was approximately 50% less potent against hemB mutants.
- A Hill-type pharmacodynamic model accurately described the observed killing activities.
Conclusions:
- The hemB mutation in S. aureus attenuates the in vitro bactericidal effect of vancomycin.
- Vancomycin efficacy against S. aureus may be influenced by specific metabolic defects, such as those in heme biosynthesis.
- Pharmacodynamic modeling provides a valuable tool for understanding antibiotic activity against bacterial mutants.
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