ArticleThe Journal of infectious diseases2015
A liaR deletion restores susceptibility to daptomycin and antimicrobial peptides in multidrug-resistant Enterococcus faecalis.
Article in The Journal of infectious diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 100 citations in OpenAlex.
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- Antimicrobial Peptides Against Antimicrobial-Resistant Bacteria: Focus on Machine Learning.Infection and drug resistance · 2026Review
- Prolonged exposure to teixobactin generates cross-tolerance to other cell wall-targeting antimicrobials inAntimicrobial agents and chemotherapy · 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
- 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
- Molecular Mechanisms of Bacterial Resistance to Antimicrobial Peptides in the Modern Era: An Updated Review.Microorganisms · 2024Review
- Arginine impacts aggregation, biofilm formation, and antibiotic susceptibility inbioRxiv : the preprint server for biology · 2024Article
- Identification ofJournal of bacteriology · 2024Article
- LiaX is a surrogate marker for cell envelope stress and daptomycin non-susceptibility inAntimicrobial agents and chemotherapy · 2024Article
- Arginine impacts aggregation, biofilm formation, and antibiotic susceptibility inFEMS microbes · 2024Article
- Short Antimicrobial Peptide Derived from the Venom Gland Transcriptome ofAntibiotics (Basel, Switzerland) · 2023Article
- Identification of DraRS inJournal of bacteriology · 2023Article
- 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
- The LiaFSR-LiaX System Mediates Resistance of Enterococcus faecium to Peptide Antibiotics and to Aureocin A53- and Enterocin L50-Like Bacteriocins.Microbiology spectrum · 2023Article
- Article
- Revisiting ESKAPE Pathogens: virulence, resistance, and combating strategies focusing on quorum sensing.Frontiers in cellular and infection microbiology · 2023Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 7 institutions in 3 countries.
Funding
Abstract
Daptomycin is a lipopeptide antibiotic that is used clinically against many gram-positive bacterial pathogens and is considered a key frontline bactericidal antibiotic to treat multidrug-resistant enterococci. Emergence of daptomycin resistance during therapy of serious enterococcal infections is a major clinical issue. In this work, we show that deletion of the gene encoding the response regulator, LiaR (a member of the LiaFSR system that controls cell envelope homeostasis), from daptomycin-resistant Enterococcus faecalis not only reversed resistance to 2 clinically available cell membrane-targeting antimicrobials (daptomycin and telavancin), but also resulted in hypersusceptibility to these antibiotics and to a variety of antimicrobial peptides of diverse origin and with different mechanisms of action. The changes in susceptibility to these antibiotics and antimicrobial peptides correlated with in vivo attenuation in a Caenorhabditis elegans model. Mechanistically, deletion of liaR altered the localization of cardiolipin microdomains in the cell membrane. Our findings suggest that LiaR is a master regulator of the enterococcal cell membrane response to diverse antimicrobial agents and peptides; as such, LiaR represents a novel target to restore the activity of clinically useful antimicrobials against these organisms and, potentially, increase susceptibility to endogenous antimicrobial peptides.
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