ArticleThe Journal of antimicrobial chemotherapy2020
A mutation in the glycosyltransferase gene lafB causes daptomycin hypersusceptibility in Enterococcus faecium.
Article in The Journal of antimicrobial chemotherapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- 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
- Article
- Exploring Daptomycin Hypersensitivity inInternational journal of molecular sciences · 2025Article
- Transcriptome analysis reveals the molecular mechanism of γ-linolenic acid eradicating the biofilm of vancomycin-resistantFrontiers in cellular and infection microbiology · 2025Article
- Biosynthesis of mitis group streptococcal glycolipids and their roles in physiology and antibiotic susceptibility.bioRxiv : the preprint server for biology · 2024Article
- Fitness Trade-Offs between Phage and Antibiotic Sensitivity in Phage-Resistant Variants: Molecular Action and Insights into Clinical Applications for Phage Therapy.International journal of molecular sciences · 2023Review
- Antimicrobial Activity of an Fmoc-Plantaricin 149 Derivative Peptide against Multidrug-Resistant Bacteria.Antibiotics (Basel, Switzerland) · 2023Article
- Occurrence ofGenes · 2022Article
- Dismantling the bacterial glycocalyx: Chemical tools to probe, perturb, and image bacterial glycans.Bioorganic & medicinal chemistry · 2021Review
- Lytic bacteriophages facilitate antibiotic sensitization ofAntimicrobial agents and chemotherapy · 2021Article
- Article
- Evolution of vancomycin-resistantProceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
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Authors and funding
7 authors at 6 institutions in 2 countries.
Funding
Abstract
objectivesTo verify dissemination of daptomycin-non-susceptible Enterococcus faecium in a hospital where daptomycin was not in use and to understand the evolutionary pathways connecting daptomycin hypersusceptibility to non-susceptibility.
methodsClonality of 26 E. faecium was assessed by PFGE and the STs of these isolates were determined. The most daptomycin-susceptible isolate was evolved in vitro by stepwise daptomycin selection, generating isolates for genome comparisons.
resultsThe spread of a high-risk daptomycin-non-susceptible VRE clone was detected, as was the occurrence of an unusual daptomycin-hypersusceptible strain (HBSJRP18). To determine the basis for daptomycin hypersusceptibility, we evolved HBSJRP18 in vitro and identified candidate genetic alterations potentially related to daptomycin susceptibility. Both lafB, encoding glycosyltransferase, which is putatively involved in lipoteichoic acid (LTA) biosynthesis, and dak, encoding a dihydroxyacetone kinase likely involved in fatty acid metabolism, were mutated in multiple independent experiments. Trans-complementation showed that the lafB polymorphism naturally occurring in HBSJRP18 caused its daptomycin hypersusceptibility. Fourier-transform infrared spectroscopy identified differences between the extracted LTA spectra from the hypersusceptible isolate and its revertant, as well as other non-susceptible variants, supporting a role for LafB in E. faecium LTA biosynthesis. Zeta potential difference was detected in one evolved dak mutant derivative. While much more susceptible to daptomycin, HBSJRP18 showed enhanced growth in the presence of piperacillin, suggesting that this, or another cell wall-targeting antibiotic, may have selected for the daptomycin-hypersusceptible phenotype.
conclusionsOur findings provide new information on the basis for daptomycin susceptibility in E. faecium, with implications for limiting the development and spread of daptomycin resistance.
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