ArticleAntimicrobial agents and chemotherapy2014
Whole-genome analyses of Enterococcus faecium isolates with diverse daptomycin MICs.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed, 145 citations in OpenAlex.
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- Therapeutic approach to difficult-to-treat multidrug-resistant enterococcal infections.Antimicrobial agents and chemotherapy · 2025Review
- Genomic insights into the spread of vancomycin- and tigecycline-resistant Enterococcus faecium ST117.Annals of clinical microbiology and antimicrobials · 2025Article
- Resistance to last-resort antibiotics in enterococci.FEMS microbiology reviews · 2025Review
- Comparative Efficacy of High-Dose Daptomycin Monotherapy versus Combination Therapy for Daptomycin-ResistantInfection and drug resistance · 2025Article
- Sentinel Surveillance reveals phylogenetic diversity and detection of linear plasmids harboringAntimicrobial agents and chemotherapy · 2024Article
- Enterococcus faecium: evolution, adaptation, pathogenesis and emerging therapeutics.Nature reviews. Microbiology · 2024Review
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- Persistence of Daptomycin-Resistant and Vancomycin-Resistant Enterococci in Hospitalized Patients with Underlying Malignancies: A 7-Year Follow-Up Study.Microorganisms · 2024Article
- Reversion to sensitivity explains limited transmission of resistance in a hospital pathogen.bioRxiv : the preprint server for biology · 2024Article
- Multidrug-resistant Enterococcus faecium strains enter the Norwegian marine environment through treated sewage.MicrobiologyOpen · 2024Article
- LiaX is a surrogate marker for cell envelope stress and daptomycin non-susceptibility inAntimicrobial agents and chemotherapy · 2024Article
- Boosting Fitness Costs Associated with Antibiotic Resistance in the Gut: On the Way to Biorestoration of Susceptible Populations.Biomolecules · 2024Review
- Insights into Kinases of ESKAPE Pathogens for Therapeutic Interventions.Cardiovascular & hematological agents in medicinal chemistry · 2024Review
- Characterization of a Tigecycline-, Linezolid- and Vancomycin-Resistant Clinical Enteroccoccus faecium Isolate, Carrying vanA and vanB Genes.Infectious diseases and therapy · 2023Article
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- Phage-Antibiotic Cocktail Rescues Daptomycin and Phage Susceptibility against Daptomycin-Nonsusceptible Enterococcus faecium in a Simulated Endocardial VegetationMicrobiology spectrum · 2023Article
- The LiaFSR-LiaX System Mediates Resistance of Enterococcus faecium to Peptide Antibiotics and to Aureocin A53- and Enterocin L50-Like Bacteriocins.Microbiology spectrum · 2023Article
34 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
Daptomycin (DAP) is a lipopeptide antibiotic frequently used as a "last-resort" antibiotic against vancomycin-resistant Enterococcus faecium (VRE). However, an important limitation for DAP therapy against VRE is the emergence of resistance during therapy. Mutations in regulatory systems involved in cell envelope homeostasis are postulated to be important mediators of DAP resistance in E. faecium. Thus, in order to gain insights into the genetic bases of DAP resistance in E. faecium, we investigated the presence of changes in 43 predicted proteins previously associated with DAP resistance in enterococci and staphylococci using the genomes of 19 E. faecium with different DAP MICs (range, 3 to 48 μg/ml). Bodipy-DAP (BDP-DAP) binding to the cell membrane assays and time-kill curves (DAP alone and with ampicillin) were performed. Genetic changes involving two major pathways were identified: (i) LiaFSR, a regulatory system associated with the cell envelope stress response, and (ii) YycFGHIJ, a system involved in the regulation of cell wall homeostasis. Thr120 → Ala and Trp73 → Cys substitutions in LiaS and LiaR, respectively, were the most common changes identified. DAP bactericidal activity was abolished in the presence of liaFSR or yycFGHIJ mutations regardless of the DAP MIC and was restored in the presence of ampicillin, but only in representatives of the LiaFSR pathway. Reduced binding of BDP-DAP to the cell surface was the predominant finding correlating with resistance in isolates with DAP MICs above the susceptibility breakpoint. Our findings suggest that genotypic information may be crucial to predict response to DAP plus β-lactam combinations and continue to question the DAP breakpoint of 4 μg/ml.
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