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Correlation of Daptomycin Bactericidal Activity and Membrane Depolarization in Staphylococcus aureus
Open accessAbstract
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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Citations
Cited by
Intrinsic and acquired resistance mechanisms in enterococcus
Hollenbeck, B. L., & Rice, L. B. (2012) · Virulence · doi:10.4161/viru.21282 · Cited by 795
Antibiotic efficacy is linked to bacterial cellular respiration
Lobritz, M. A., Belenky, P., Porter, C. B. M., Gutierrez, A., Yang, J. H., Schwarz, E. G., Dwyer, D. J., Khalil, A. S., & Collins, J. J. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1509743112 · Cited by 773
Daptomycin: a lipopeptide antibiotic for the treatment of serious Gram-positive infections
Steenbergen, J. N., Alder, J., Thorne, G. M., & Tally, F. P. (2005) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkh546 · Cited by 561
Inhibition of Daptomycin by Pulmonary Surfactant: In Vitro Modeling and Clinical Impact
Silverman, J. A., Mortin, L. I., VanPraagh, A. D. G., Li, T., & Alder, J. (2005) · The Journal of Infectious Diseases · doi:10.1086/430352 · Cited by 541
Self-citationPogliano, J., Pogliano, N., & Silverman, J. A. (2012) · Journal of Bacteriology · doi:10.1128/jb.00011-12 · Cited by 319
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Metadata
- Authors
- Silverman, J. A., Perlmutter, N. G., & Shapiro, H. M.
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- 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).
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