ArticleNucleic acids research2015
A variable DNA recognition site organization establishes the LiaR-mediated cell envelope stress response of enterococci to daptomycin.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 41 citations in OpenAlex.
- Molecular Regulation of Virulence and Dental Biofilm Formation in Streptococcus mutans: Unravelling the Crosstalk Between the VicRK and LiaSR Two-Component Systems.Molecular oral microbiology · 2026Review
- Subtractive Proteomics-Based Prioritization of Drug Targets in Enterococcus faecalis V583 and Structure-Based Identification of Plant-Derived Inhibitors Targeting Alanine Racemase: A High Priority Target.Molecular biotechnology · 2026Article
- LiaS-dependent activation of the MadR regulon enables cross-talk betweenbioRxiv : the preprint server for biology · 2025Article
- Resistance to last-resort antibiotics in enterococci.FEMS microbiology reviews · 2025Review
- LiaR-dependent gene expression contributes to antimicrobial responses in group AAntimicrobial agents and chemotherapy · 2024Article
- Two distinct regulatory systems control pulcherrimin biosynthesis in Bacillus subtilis.PLoS genetics · 2024Article
- Two Distinct Regulatory Systems Control Pulcherrimin Biosynthesis inbioRxiv : the preprint server for biology · 2024Article
- The LiaFSR-LiaX System Mediates Resistance of Enterococcus faecium to Peptide Antibiotics and to Aureocin A53- and Enterocin L50-Like Bacteriocins.Microbiology spectrum · 2023Article
- Structural and biochemical analyses of the flagellar expression regulator DegU from Listeria monocytogenes.Scientific reports · 2022Article
- Structural insights into DNA binding domain of vancomycin-resistance-associated response regulator in complex with its promoter DNA from Staphylococcus aureus.Protein science : a publication of the Protein Society · 2022Article
- Resistance in Vancomycin-Resistant Enterococci.Infectious disease clinics of North America · 2020Review
- Tools to map target genes of bacterial two-component system response regulators.Environmental microbiology reports · 2020Review
- Low phosphatase activity of LiaS and strong LiaR-DNA affinity explain the unusual LiaS to LiaR in vivo stoichiometry.BMC microbiology · 2020Article
- Antibiotic Production and Antibiotic Resistance: The Two Sides of AbrB1/B2, a Two-Component System ofFrontiers in microbiology · 2020Article
- Environment Shapes the Accessible Daptomycin Resistance Mechanisms in Enterococcus faecium.Antimicrobial agents and chemotherapy · 2019Article
- Disrupting Membrane Adaptation Restores In Vivo Efficacy of Antibiotics Against Multidrug-Resistant Enterococci and Potentiates Killing by Human Neutrophils.The Journal of infectious diseases · 2019Article
- Two Mutations Commonly Associated with Daptomycin Resistance in Enterococcus faecium LiaSBiochemistry · 2018Article
- Article
- Membrane adaptation limitations inRSC advances · 2018Article
- Using experimental evolution to identify druggable targets that could inhibit the evolution of antimicrobial resistance.The Journal of antibiotics · 2018Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
LiaR is a 'master regulator' of the cell envelope stress response in enterococci and many other Gram-positive organisms. Mutations to liaR can lead to antibiotic resistance to a variety of antibiotics including the cyclic lipopeptide daptomycin. LiaR is phosphorylated in response to membrane stress to regulate downstream target operons. Using DNA footprinting of the regions upstream of the liaXYZ and liaFSR operons we show that LiaR binds an extended stretch of DNA that extends beyond the proposed canonical consensus sequence suggesting a more complex level of regulatory control of target operons. We go on to determine the biochemical and structural basis for increased resistance to daptomycin by the adaptive mutation to LiaR (D191N) first identified from the pathogen Enterococcus faecalis S613. LiaR(D191N) increases oligomerization of LiaR to form a constitutively activated tetramer that has high affinity for DNA even in the absence of phosphorylation leading to increased resistance. Crystal structures of the LiaR DNA binding domain complexed to the putative consensus sequence as well as an adjoining secondary sequence show that upon binding, LiaR induces DNA bending that is consistent with increased recruitment of RNA polymerase to the transcription start site and upregulation of target operons.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.