ArticleAntimicrobial agents and chemotherapy2013
Biochemical characterization of cardiolipin synthase mutations associated with daptomycin resistance in enterococci.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 89 citations in OpenAlex.
- Revealing the Fate of Isomeric Monounsaturated Fatty Acids inACS infectious diseases · 2026Article
- A two-component system signaling hub controls enterococcal membrane remodeling in response to daptomycin.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A Daptomycin Resistance-Conferring cls1 I269T Mutation in Enterococcus faecium and its Global Prevalence.Current microbiology · 2026Article
- Article
- Daptomycin forms a stable complex with phosphatidylglycerol for selective uptake to bacterial membrane.eLife · 2025Article
- Resistance to last-resort antibiotics in enterococci.FEMS microbiology reviews · 2025Review
- Molecular basis of cell membrane adaptation in daptomycin-resistant Enterococcus faecalis.JCI insight · 2024Article
- Simvastatin induces human gut bacterial cell surface genes.Molecular microbiology · 2024Article
- Top-Down Genomic Surveillance Approach To Investigate the Genomic Epidemiology and Antibiotic Resistance Patterns of Enterococcus faecium Detected in Cancer Patients in Arkansas.Microbiology spectrum · 2023Article
- Membrane properties modulation by SanA: implications for xenobiotic resistance inFrontiers in microbiology · 2023Article
- Evolution of Enterococcus faecium in Response to a Combination of Daptomycin and Fosfomycin Reveals Distinct and Diverse Adaptive Strategies.Antimicrobial agents and chemotherapy · 2022Article
- An orally administered drug prevents selection for antibiotic-resistant bacteria in the gut during daptomycin therapy.Evolution, medicine, and public health · 2022Article
- New Mutations inFrontiers in microbiology · 2022Article
- Daptomycin Resistance in Enterococcus faecium Can Be Delayed by Disruption of the LiaFSR Stress Response Pathway.Antimicrobial agents and chemotherapy · 2021Article
- Article
- Genomic Insights Into Last-Line Antimicrobial Resistance in Multidrug-ResistantFrontiers in microbiology · 2021Review
- Impact of Daptomycin Dose Exposure Alone or in Combination with β-Lactams or Rifampin against Vancomycin-Resistant Enterococci in anAntimicrobial agents and chemotherapy · 2020Article
- Article
- Environment Shapes the Accessible Daptomycin Resistance Mechanisms in Enterococcus faecium.Antimicrobial agents and chemotherapy · 2019Article
- Comparison of Antibiotic Resistance Mechanisms in Antibiotic-Producing and Pathogenic Bacteria.Molecules (Basel, Switzerland) · 2019Review
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Daptomycin (DAP) resistance in enterococci has been linked to mutations in genes that alter the cell envelope stress response (CESR) (liaFSR) and changes in enzymes that directly affect phospholipid homeostasis, and these changes may alter membrane composition, such as that of cardiolipin synthase (Cls). While Cls substitutions are observed in response to DAP therapy, the effect of these mutations on Cls activity remains obscure. We have expressed, purified, and characterized Cls enzymes from both Enterococcus faecium S447 (residues 52 to 482; Cls447a) and Enterococcus faecalis S613 (residues 53 to 483; Cls613a) as well as Cls variants harboring a single-amino-acid change derived from DAP-resistant isolates of E. faecium. E. faecium Cls447a and E. faecalis Cls613a are tightly associated with the membrane and copurify with their substrate, phosphatidylglycerol (PG), and product, cardiolipin (CL). The amount of PG that copurifies with Cls is in molar excess to protein, suggesting that the enzyme localizes to PG-rich membrane regions. Both Cls447a(H215R) and Cls447a(R218Q) showed an increase in V(max) (μM CL/min/μM protein) from 0.16 ± 0.01 to 0.26 ± 0.02 and 0.26 ± 0.04, respectively, indicating that mutations associated with adaptation to DAP increase Cls activity. Modeling of Cls447a to Streptomyces sp. phospholipase D indicates that the adaptive mutations Cls447a(H215R) and Cls447a(R218Q) are proximal to the phospholipase domain 1 (PLD1) active site and near the putative nucleophile H217. As mutations to Cls are part of a larger genomic adaptation process, increased Cls activity is likely to be highly epistatic with other changes to facilitate DAP resistance.
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