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Correlation of Daptomycin Bactericidal Activity and Membrane Depolarization in Staphylococcus aureus

Open access
Silverman, Jared A., Perlmutter, Nancy G., Shapiro, Howard M.·2003·Antimicrobial Agents and Chemotherapy

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 μg/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.

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Metadata

Authors
Silverman, J. A., Perlmutter, N. G., & Shapiro, H. M.
Venue
Antimicrobial Agents and Chemotherapy
Published
2003-08
Volume
47
Issue
8
Pages
2538-2544
ISSN
  • 0066-4804 (ISSN-L)
  • 1098-6596
OpenAlex
W2115550568
Cited by
656
References
0
FWCI
12.84
Type
journal article
Language
en
Open access
green

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Silverman, J. A., Perlmutter, N. G., & Shapiro, H. M. (2003). Correlation of Daptomycin Bactericidal Activity and Membrane Depolarization in Staphylococcus aureus. Antimicrobial Agents and Chemotherapy. https://doi.org/10.1128/aac.47.8.2538-2544.2003

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.