ArticleMolecular microbiology2019
LiaR-independent pathways to daptomycin resistance in Enterococcus faecalis reveal a multilayer defense against cell envelope antibiotics.
Article in Molecular microbiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 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
- Vancomycin resistance in gram-positive infections: evolutionary strategies of survival.Archives of microbiology · 2026Review
- Article
- Unexpected contribution of the Fak system and the thioesterase TesE to the growth and membrane physiology ofJournal of bacteriology · 2025Article
- LiaS-dependent activation of the MadR regulon enables cross-talk betweenbioRxiv : the preprint server for biology · 2025Article
- Membrane Lipids Augment Cell Envelope Stress Signaling via the MadRS System to Defend Against Antimicrobial Peptides and Antibiotics in Enterococcus faecalis.The Journal of infectious diseases · 2025Article
- Repurposing fusidic acid as an antimicrobial against enterococci with a low probability of resistance development.International microbiology : the official journal of the Spanish Society for Microbiology · 2024Article
- Sentinel Surveillance reveals phylogenetic diversity and detection of linear plasmids harboringAntimicrobial agents and chemotherapy · 2024Article
- The HtrA chaperone monitors sortase-assembled pilus biogenesis in Enterococcus faecalis.PLoS genetics · 2024Article
- Guarding the walls: the multifaceted roles of Bce modules in cell envelope stress sensing and antimicrobial resistance.Journal of bacteriology · 2024Review
- Membrane Lipids Augment Cell Envelope Stress Signaling and Resistance to Antibiotics and Antimicrobial Peptides inbioRxiv : the preprint server for biology · 2023Article
- Phage-Antibiotic Cocktail Rescues Daptomycin and Phage Susceptibility against Daptomycin-Nonsusceptible Enterococcus faecium in a Simulated Endocardial VegetationMicrobiology spectrum · 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
- Contemporary Clinical and Molecular Epidemiology of Vancomycin-Resistant Enterococcal Bacteremia: A Prospective Multicenter Cohort Study (VENOUS I).Open forum infectious diseases · 2022Article
- Bacterial cell membranes and their role in daptomycin resistance: A review.Frontiers in molecular biosciences · 2022Review
- Daptomycin Resistance in Enterococcus faecium Can Be Delayed by Disruption of the LiaFSR Stress Response Pathway.Antimicrobial agents and chemotherapy · 2021Article
- Adaptive evolution of hybrid bacteria by horizontal gene transfer.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Apparent nosocomial adaptation of Enterococcus faecalis predates the modern hospital era.Nature communications · 2021Article
- Removal of peptidoglycan and inhibition of active cellular processes leads to daptomycin tolerance in Enterococcus faecalis.PloS one · 2021Article
- Sentinel Surveillance Reveals Emerging Daptomycin-Resistant ST736Frontiers in microbiology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The lipopeptide antibiotic daptomycin (DAP) is a key drug against serious enterococcal infections, but the emergence of resistance in the clinical setting is a major concern. The LiaFSR system plays a prominent role in the development of DAP resistance (DAP-R) in enterococci, and blocking this stress response system has been proposed as a novel therapeutic strategy. In this work, we identify LiaR-independent pathways in Enterococcus faecalis that regulate cell membrane adaptation in response to antibiotics. We adapted E. faecalis OG1RF (a laboratory strain) and S613TM (a clinical strain) lacking liaR to increasing concentrations of DAP, leading to the development of DAP-R and elevated MICs to bacitracin and ceftriaxone. Whole genome sequencing identified changes in the YxdJK two-component regulatory system and a putative fatty acid kinase (dak) in both DAP-R strains. Deletion of the gene encoding the YxdJ response regulator in both the DAP-R mutant and wild-type OG1RF decreased MICs to DAP, even when a functional LiaFSR system was present. Mutations in dak were associated with slower growth, decreased membrane fluidity and alterations of cell morphology. These findings suggest that overlapping stress response pathways can provide protection against antimicrobial peptides in E. faecalis at a significant cost in bacterial fitness.
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