ArticleAntimicrobial agents and chemotherapy2013
In vivo studies suggest that induction of VanS-dependent vancomycin resistance requires binding of the drug to D-Ala-D-Ala termini in the peptidoglycan cell wall.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 45 citations in OpenAlex.
- Methicillin-resistant Staphylococcus aureus.Nature reviews. Disease primers · 2026Review
- Emergence, evolution, and global dissemination of antimicrobial resistance: A One Health review.Archives of microbiology · 2026Review
- Article
- Methicillin-resistant and susceptible Staphylococcus aureus: tolerance, immune evasion and treatment.Nature reviews. Microbiology · 2026Review
- Unveiling the synergistic power of 3-hydrazinoquinoxaline-2-thiol and vancomycin against MRSA: AnBiomolecules & biomedicine · 2025Article
- Insights into Kinases of ESKAPE Pathogens for Therapeutic Interventions.Cardiovascular & hematological agents in medicinal chemistry · 2024Review
- Heterologous Expression Reveals Ancient Properties of Tei3—A VanS Ortholog from the Teicoplanin Producer Actinoplanes teichomyceticusInternational journal of molecular sciences · 2022Article
- Two-Component Systems ofInternational journal of molecular sciences · 2022Review
- VanG- and D-Ala-D-Ser-dependent peptidoglycan synthesis and vancomycin resistance in Clostridioides difficile.Molecular microbiology · 2022Article
- Regulation of Resistance in Vancomycin-Resistant Enterococci: The VanRS Two-Component System.Microorganisms · 2021Review
- Membrane Sensor Histidine Kinases: Insights from Structural, Ligand and Inhibitor Studies of Full-Length Proteins and Signalling Domains for Antibiotic Discovery.Molecules (Basel, Switzerland) · 2021Review
- Next-Generation Total Synthesis of Vancomycin.Journal of the American Chemical Society · 2020Article
- Molecular mechanisms of vancomycin resistance.Protein science : a publication of the Protein Society · 2020Review
- Article
- Trichlorination of a Teicoplanin-Type Glycopeptide Antibiotic by the Halogenase StaI Evades Resistance.Antimicrobial agents and chemotherapy · 2018Article
- Genome sequencing analysis of Streptomyces coelicolor mutants that overcome the phosphate-depending vancomycin lethal effect.BMC genomics · 2018Article
- Specificity of Induction of Glycopeptide Antibiotic Resistance in the Producing Actinomycetes.Antibiotics (Basel, Switzerland) · 2018Article
- Antimicrobial resistance (AMR) nanomachines-mechanisms for fluoroquinolone and glycopeptide recognition, efflux and/or deactivation.Biophysical reviews · 2018Review
- Essential Two-Component Systems Regulating Cell Envelope Functions: Opportunities for Novel Antibiotic Therapies.The Journal of membrane biology · 2018Review
- Characterisation of the selective binding of antibiotics vancomycin and teicoplanin by the VanS receptor regulating type A vancomycin resistance in the enterococci.Biochimica et biophysica acta. General subjects · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
VanRS two-component regulatory systems are key elements required for the transcriptional activation of inducible vancomycin resistance genes in bacteria, but the precise nature of the ligand signal that activates these systems has remained undefined. Using the resistance system in Streptomyces coelicolor as a model, we have undertaken a series of in vivo studies which indicate that the VanS sensor kinase in VanB-type resistance systems is activated by vancomycin in complex with the d-alanyl-d-alanine (d-Ala-d-Ala) termini of cell wall peptidoglycan (PG) precursors. Complementation of an essential d-Ala-d-Ala ligase activity by constitutive expression of vanA encoding a bifunctional d-Ala-d-Ala and d-alanyl-d-lactate (d-Ala-d-Lac) ligase activity allowed construction of strains that synthesized variable amounts of PG precursors containing d-Ala-d-Ala. Assays quantifying the expression of genes under VanRS control showed that the response to vancomycin in these strains correlated with the abundance of d-Ala-d-Ala-containing PG precursors; strains producing a lower proportion of PG precursors terminating in d-Ala-d-Ala consistently exhibited a lower response to vancomycin. Pretreatment of wild-type cells with vancomycin or teicoplanin to saturate and mask the d-Ala-d-Ala binding sites in nascent PG also blocked the transcriptional response to subsequent vancomycin exposure, and desleucyl vancomycin, a vancomycin analogue incapable of interacting with d-Ala-d-Ala residues, failed to induce van gene expression. Activation of resistance by a vancomycin-d-Ala-d-Ala PG complex predicts a limit to the proportion of PG that can be derived from precursors terminating in d-Ala-d-Lac, a restriction also enforced by the bifunctional activity of the VanA ligase.
Indexed as
Identifiers
What OpenQuestion holds
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.