The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
Daptomycin-Mediated Reorganization of Membrane Architecture Causes Mislocalization of Essential Cell Division Proteins
Open accessAbstract
Daptomycin is a lipopeptide antibiotic used clinically for the treatment of certain types of Gram-positive infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA). Details of the mechanism of action of daptomycin continue to be elucidated, particularly the question of whether daptomycin acts on the cell membrane, the cell wall, or both. Here, we use fluorescence microscopy to directly visualize the interaction of daptomycin with the model Gram-positive bacterium Bacillus subtilis. We show that the first observable cellular effects are the formation of membrane distortions (patches of membrane) that precede cell death by more than 30 min. Membrane patches are able to recruit the essential cell division protein DivIVA. Recruitment of DivIVA correlates with membrane defects and changes in cell morphology, suggesting a localized alteration in the activity of enzymes involved in cell wall synthesis that could account for previously described effects of daptomycin on cell wall morphology and septation. Membrane defects colocalize with fluorescently labeled daptomycin, DivIVA, and fluorescent reporters of peptidoglycan biogenesis (Bocillin FL and BODIPY FL-vancomycin), suggesting that daptomycin plays a direct role in these events. Our results support a mechanism for daptomycin with a primary effect on cell membranes that in turn redirects the localization of proteins involved in cell division and cell wall synthesis, causing dramatic cell wall and membrane defects, which may ultimately lead to a breach in the cell membrane and cell death. These results help resolve the longstanding questions regarding the mechanism of action of this important class of antibiotics.
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“Of note, recent evidence suggests that DAP mainly targets the CM at the level of the division septum (86).”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [86]
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“In addition, the stationary growth-phase conditions make it less likely that bacterial cell wall-active antibiotics (β-lactams and glycopeptides) are optimally effective.[77][78][79]”
From Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association (2015) · cites this paper as [78]
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Cites
Membrane curvature and mechanisms of dynamic cell membrane remodelling
McMahon, H. T., & Gallop, J. L. (2005) · Nature · doi:10.1038/nature04396 · Cited by 2,205
Control of Cell Morphogenesis in Bacteria
Daniel, R. A., & Errington, J. (2003) · Cell · doi:10.1016/s0092-8674(03)00421-5 · Cited by 740
Regulation of endospore formation in Bacillus subtilis
Errington, J. (2003) · Nature Reviews Microbiology · doi:10.1038/nrmicro750 · Cited by 712
Correlation of Daptomycin Bactericidal Activity and Membrane Depolarization in Staphylococcus aureus
Silverman, J. A., Perlmutter, N. G., & Shapiro, H. M. (2003) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.47.8.2538-2544.2003 · Cited by 657
Self-citationBacterial viability and antibiotic susceptibility testing with SYTOX green nucleic acid stain
Roth, B. L., Poot, M., Yue, S. T., & Millard, P. J. (1997) · Applied and Environmental Microbiology · doi:10.1128/aem.63.6.2421-2431.1997 · Cited by 583
Membrane potential is important for bacterial cell division
Strahl, H., & Hamoen, L. W. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1005485107 · Cited by 572
Sterlini, J. M., & Mandelstam, J. (1969) · Biochemical Journal · doi:10.1042/bj1130029 · Cited by 559
Genetic Changes That Correlate with Reduced Susceptibility to Daptomycin in Staphylococcus aureus
Friedman, L., Alder, J. D., & Silverman, J. A. (2006) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00039-06 · Cited by 454
Self-citationStraus, S. K., & Hancock, R. E. W. (2006) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2006.02.009 · Cited by 446
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Research works printed but not linked: 1
- Ryter, 1965, Etude morphologie de la sporulation de Bacillus subtilis, Ann. Inst. Pasteur (Paris), 108, 40
Cited by
Sorted by citations
Baddour, L. M., Wilson, W. R., Bayer, A. S., Fowler, V. G., Tleyjeh, I. M., Rybak, M. J., Barsic, B., Lockhart, P. B., Gewitz, M. H., Levison, M. E., et al. (2015) · Circulation · doi:10.1161/cir.0000000000000296 · Cited by 3,232
Mechanisms of Antibiotic Resistance
Munita, J. M., & Arias, C. A. (2016) · Microbiology Spectrum · doi:10.1128/microbiolspec.vmbf-0016-2015 · Cited by 2,782
Mechanisms of antibiotic resistance in enterococci
Miller, W. R., Munita, J. M., & Arias, C. A. (2014) · Expert Review of Anti-infective Therapy · doi:10.1586/14787210.2014.956092 · Cited by 772
Molecular mechanisms of membrane targeting antibiotics
Epand, R. M., Walker, C., Epand, R. F., & Magarvey, N. A. (2015) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2015.10.018 · Cited by 701
The Evolving Role of Chemical Synthesis in Antibacterial Drug Discovery
Wright, P. M., Seiple, I. B., & Myers, A. G. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201310843 · Cited by 428
Metadata
- Authors
- Pogliano, J., Pogliano, N., & Silverman, J. A.
- Affiliations
- University of California San Diego (US)
- Cubist Pharmaceuticals (United States) (US)
- ORCID
- Pogliano, J.
- Venue
- Journal of Bacteriology
- Publisher
- American Society for Microbiology
- Published
- 2012-06-01
- Volume
- 194
- Issue
- 17
- Pages
- 4494-4504
- ISSN
- 0021-9193 (ISSN-L)
- PMC
- PMC3415520
- OpenAlex
- W2113063737
- Cited by
- 319
- References
- 59
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 23 · 2023: 19 · 2022: 23 · 2021: 22 · 2020: 27 · 2019: 27 · 2018: 23 · 2017: 30 · 2016: 30 · 2015: 29 · 2014: 25 · 2013: 18 · 2012: 5
- FWCI
- 14.84
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Bacteriology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM073898, GM073898)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Keywords
- daptomycin, antibiotic mechanism of action, membrane deformation, DivIVA, cell division proteins, cell wall biosynthesis, Bacillus subtilis, methicillin-resistant Staphylococcus aureus, cell morphology, septation
- MeSH terms
- Anti-Bacterial Agents, Bacillus subtilis, Bacterial Proteins, Cell Division, Cell Membrane, Cell Wall, Microbial Sensitivity Tests, Microscopy, Fluorescence, Peptidoglycan, Daptomycin, Cell Cycle Proteins
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