The DOI matches its Crossref record; 36 of the 37 references it cites were found in a registry or an index.
Genetic Basis for In Vivo Daptomycin Resistance in Enterococci
Open accessAbstract
BACKGROUND: Daptomycin is a lipopeptide with bactericidal activity that acts on the cell membrane of enterococci and is often used off-label to treat patients infected with vancomycin-resistant enterococci. However, the emergence of resistance to daptomycin during therapy threatens its usefulness. METHODS: We performed whole-genome sequencing and characterization of the cell envelope of a clinical pair of vancomycin-resistant Enterococcus faecalis isolates from the blood of a patient with fatal bacteremia; one isolate (S613) was from blood drawn before treatment and the other isolate (R712) was from blood drawn after treatment with daptomycin. The minimal inhibitory concentrations (MICs) of these two isolates were 1 and 12 μg per milliliter, respectively. Gene replacements were made to exchange the alleles found in isolate S613 with those in isolate R712. RESULTS: Isolate R712 had in-frame deletions in three genes. Two genes encoded putative enzymes involved in phospholipid metabolism, GdpD (which denotes glycerophosphoryl diester phosphodiesterase) and Cls (which denotes cardiolipin synthetase), and one gene encoded a putative membrane protein, LiaF (which denotes lipid II cycle-interfering antibiotics protein but whose exact function is not known). LiaF is predicted to be a member of a three-component regulatory system (LiaFSR) involved in the stress-sensing response of the cell envelope to antibiotics. Replacement of the liaF allele of isolate S613 with the liaF allele from isolate R712 quadrupled the MIC of daptomycin, whereas replacement of the gdpD allele had no effect on MIC. Replacement of both the liaF and gdpD alleles of isolate S613 with the liaF and gdpD alleles of isolate R712 raised the daptomycin MIC for isolate S613 to 12 μg per milliliter. As compared with isolate S613, isolate R712--the daptomycin-resistant isolate--had changes in the structure of the cell envelope and alterations in membrane permeability and membrane potential. CONCLUSIONS: Mutations in genes encoding LiaF and a GdpD-family protein were necessary and sufficient for the development of resistance to daptomycin during the treatment of vancomycin-resistant enterococci. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health.).
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“In enterococci, work using whole genome sequencing of a clinical strain-pair of E. faecalis that developed DAP resistance (DAP-R) over the course of therapy, revealed that changes in a three-component regulatory system designated LiaFSR (which orchestrates the cell-envelope stress response in gram-positives) are paramount in the development of DAP-R (88).”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [88]
In the citing paper
“For example, two enzymes, a glycerol-phosphodiester phosphodiesterase (GdpD) and cardiolipin synthase (Cls) were found to enhance the DAP-R phenotype in the background of liaFSR mutations in E. faecalis (88).”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [88]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Velvet: Algorithms for de novo short read assembly using de Bruijn graphsPreprint
Zerbino, D. R., & Birney, E. (2008) · Genome Research · doi:10.1101/gr.074492.107 · Cited by 9,575
Bad Bugs, No Drugs: No ESKAPE! An Update from the Infectious Diseases Society of America
Boucher, H. W., Talbot, G. H., Bradley, J. S., Edwards, J. E., Gilbert, D. N., Rice, L. B., Scheld, M., Spellberg, B. J., & Bartlett, J. (2008) · Clinical Infectious Diseases · doi:10.1086/595011 · Cited by 5,092
Performance Standards for Antimicrobial Susceptibility Testing; Eighteenth Informational Supplement
Cockerill, F. R., & Clinical (2008) · Medical Entomology and Zoology · Cited by 2,065
Principles and Techniques of Electron Microscopy: Biological Applications
Maugel, T. K., & Hayat, M. A. (1979) · Transactions of the American Microscopical Society · doi:10.2307/3226038 · Cited by 1,327
Mwangi, M. M., Wu, S. W., Zhou, Y., Sieradzki, K., de LENCASTRE, H., Richardson, P., Bruce, D. G., Rubin, E. M., Myers, E. W., Siggia, E. D., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0609839104 · Cited by 538
DiazGranados, C. A., Zimmer, S. M., Mitchel, K., & Jernigan, J. A. (2005) · Clinical Infectious Diseases · doi:10.1086/430909 · Cited by 459
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
Cardiolipin membrane domains in prokaryotes and eukaryotes
Mileykovskaya, E., & Dowhan, W. (2009) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2009.04.003 · Cited by 402
Principles and Techniques of Electron Microscopy: Biological Applications
Maugel, T. K., & Hayat, M. A. (1977) · Transactions of the American Microscopical Society · doi:10.2307/3226107 · Cited by 389
Ernst, C. M., Neumann‐Staubitz, P., Mishra, N. N., Yang, S. J., Hornig, G., Kalbacher, H., Bayer, A. S., Kraus, D., & Peschel, A. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000660 · Cited by 370
Research works printed but not linked: 1
- 10.1099/mic.0. 2006/003111-0 · DOI
Cited by
Sorted by citations
Mechanisms of Antibiotic Resistance
Munita, J. M., & Arias, C. A. (2016) · Microbiology Spectrum · doi:10.1128/microbiolspec.vmbf-0016-2015 · Cited by 2,782
Self-citationThe rise of the Enterococcus: beyond vancomycin resistance
Arias, C. A., & Murray, B. E. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2761 · Cited by 1,776
Self-citationESKAPE pathogens: antimicrobial resistance, epidemiology, clinical impact and therapeutics
Miller, W. R., & Arias, C. A. (2024) · Nature Reviews Microbiology · doi:10.1038/s41579-024-01054-w · Cited by 920
Self-citationSnitkin, E. S., Zelazny, A. M., Thomas, P. J., Stock, F., Program, N. C. S., Henderson, D. K., Palmore, T. N., & Segre, J. A. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004129 · Cited by 863
Intrinsic and acquired resistance mechanisms in enterococcus
Hollenbeck, B. L., & Rice, L. B. (2012) · Virulence · doi:10.4161/viru.21282 · Cited by 795
Metadata
- Authors
- Arias, C. A., Panesso, D., McGrath, D. M., Qin, X., Mojica, M. F., Miller, C., Diaz, L., Tran, T. T., Rincon, S., Barbu, E. M., Reyes, J., Roh, J. H., Lobos, E., Sodergren, E., Pasqualini, R., Arap, W., Quinn, J. P., Shamoo, Y., Murray, B. E., & Weinstock, G. M.
- Affiliations
- Universidad El Bosque (CO)
- The University of Texas MD Anderson Cancer Center (US)
- Baylor College of Medicine (US)
- Rice University (US)
- University of Houston (US)
- Washington University in St. Louis (US)
- Pfizer (United States) (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2011-09-08
- Volume
- 365
- Issue
- 10
- Pages
- 892-900
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC3205971
- OpenAlex
- W2129864306
- Cited by
- 377
- References
- 37
- Citations by year
- 2026: 17 · 2025: 20 · 2024: 20 · 2023: 22 · 2022: 20 · 2021: 18 · 2020: 35 · 2019: 18 · 2018: 20 · 2017: 21 · 2016: 32 · 2015: 33 · 2014: 35 · 2013: 28 · 2012: 32
- FWCI
- 14.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion)
- Funders
- National Human Genome Research Institute (U54HG004968)
- National Institute of Allergy and Infectious Diseases (R37AI047923, R01AI093749, R00AI072961, R01AI080714, R01AI067861)
- Topics
- Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Keywords
- daptomycin resistance, vancomycin-resistant enterococci, Enterococcus faecalis, envelope stress response, membrane permeability, membrane potential, bacteremia, gene replacement, minimum inhibitory concentration, phospholipid metabolism
- MeSH terms
- Anti-Bacterial Agents, Genes, Bacterial, Humans, Microbial Sensitivity Tests, Mutation, Enterococcus faecalis, Bacteremia, Genome, Bacterial, Gram-Positive Bacterial Infections, Sequence Analysis, DNA, Daptomycin, Vancomycin Resistance, Drug Resistance, Bacterial, Microscopy, Electron, Transmission
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
