Correlation of daptomycin bactericidal activity and membrane depolarization in Staphylococcus aureus.
Antimicrob Agents Chemother
; 47(8): 2538-44, 2003 Aug.
Article
en En
| MEDLINE
| ID: mdl-12878516
ABSTRACT
The objective of this study was to further elucidate the role of membrane potential in the mechanism of action of daptomycin, a novel lipopeptide antibiotic. Membrane depolarization was measured by both fluorimetric and flow cytometric assays. Adding daptomycin (5 micro g/ml) to Staphylococcus aureus gradually dissipated membrane potential. In both assays, cell viability was reduced by >99% and membrane potential was reduced by >90% within 30 min of adding daptomycin. Cell viability decreased in parallel with changes in membrane potential, demonstrating a temporal correlation between bactericidal activity and membrane depolarization. Decreases in viability and potential also showed a dose-dependent correlation. Depolarization is indicative of ion movement across the cytoplasmic membrane. Fluorescent probes were used to demonstrate Ca(2+)-dependent, daptomycin-triggered potassium release from S. aureus. Potassium release was also correlated with bactericidal activity. This study demonstrates a clear correlation between dissipation of membrane potential and the bactericidal activity of daptomycin. A multistep model for daptomycin's mechanism of action is proposed.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Staphylococcus aureus
/
Daptomicina
/
Antibacterianos
Idioma:
En
Revista:
Antimicrob Agents Chemother
Año:
2003
Tipo del documento:
Article
País de afiliación:
Estados Unidos