ArticleScientific reports2017
Insights into the Mechanistic Basis of Plasmid-Mediated Colistin Resistance from Crystal Structures of the Catalytic Domain of MCR-1.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 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
70 citing papers in PubMed, 138 citations in OpenAlex.
- Bacteriocins in Veterinary Medicine: From Antibiotic Limitations to Targeted Solutions.International journal of molecular sciences · 2026Review
- A Cysteine-Dependent Peptide Cyclase with Broad Substrate Tolerance Enables Chemoenzymatic Synthesis of Macolacin Analogs.ACS chemical biology · 2026Article
- Antimicrobial Effect of Spices and Their Phytochemicals: A Novel Approach to Overcoming Antibiotic Resistance.MedComm · 2026Review
- Mechanistic basis of antimicrobial resistance mediated by the phosphoethanolamine transferase MCR-1.Nature communications · 2025Article
- Colistin resistance plasmids dually enhance bacterial virulence and antibiotic resistance via surface polysaccharide biosynthesis.Nature communications · 2025Article
- Dynamic Behavior and Substrate Interactions of the Polymyxin Resistance Determinant MCR-1 Investigated by Molecular Dynamics Simulations in the Membrane Environment.Journal of chemical information and modeling · 2025Article
- Metal-Based Approaches for the Fight against Antimicrobial Resistance: Mechanisms, Opportunities, and Challenges.Journal of the American Chemical Society · 2025Review
- Article
- Artesunate, EDTA, and colistin work synergistically against MCR-negative and -positive colistin-resistanteLife · 2025Article
- Bacteria carrying mobile colistin resistance genes and their control measures, an updated review.Archives of microbiology · 2024Review
- Structure-Guided Bacteria Specificity and Wide Activity Spectrum of Endotoxin-Responsive Peptide Nanonets.Nano letters · 2024Article
- Review
- High-throughput screening identification of apigenin that reverses the colistin resistance of mcr-1-positive pathogens.Microbiology spectrum · 2024Article
- A Review on Colistin Resistance: An Antibiotic of Last Resort.Microorganisms · 2024Review
- Challenges in the Detection of Polymyxin Resistance: From Today to the Future.Microorganisms · 2024Review
- Enhancement by pyrazolones of colistin efficacy against mcr-1-expressing E. coli: an in silico and in vitro investigation.Journal of computer-aided molecular design · 2023Article
- Structural biology of MCR-1-mediated resistance to polymyxin antibiotics.Current opinion in structural biology · 2023Review
- First Report and Characterization of theMicroorganisms · 2023Article
- Untying the anchor for the lipopolysaccharide: lipid A structural modification systems offer diagnostic and therapeutic options to tackle polymyxin resistance.Arhiv za higijenu rada i toksikologiju · 2023Review
- Phosphoethanolamine Transferases as Drug Discovery Targets for Therapeutic Treatment of Multi-Drug Resistant Pathogenic Gram-Negative Bacteria.Antibiotics (Basel, Switzerland) · 2023Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 6 institutions in 3 countries.
Funding
Abstract
The polymixin colistin is a "last line" antibiotic against extensively-resistant Gram-negative bacteria. Recently, the mcr-1 gene was identified as a plasmid-mediated resistance mechanism in human and animal Enterobacteriaceae, with a wide geographical distribution and many producer strains resistant to multiple other antibiotics. mcr-1 encodes a membrane-bound enzyme catalysing phosphoethanolamine transfer onto bacterial lipid A. Here we present crystal structures revealing the MCR-1 periplasmic, catalytic domain to be a zinc metalloprotein with an alkaline phosphatase/sulphatase fold containing three disulphide bonds. One structure captures a phosphorylated form representing the first intermediate in the transfer reaction. Mutation of residues implicated in zinc or phosphoethanolamine binding, or catalytic activity, restores colistin susceptibility of recombinant E. coli. Zinc deprivation reduces colistin MICs in MCR-1-producing laboratory, environmental, animal and human E. coli. Conversely, over-expression of the disulphide isomerase DsbA increases the colistin MIC of laboratory E. coli. Preliminary density functional theory calculations on cluster models suggest a single zinc ion may be sufficient to support phosphoethanolamine transfer. These data demonstrate the importance of zinc and disulphide bonds to MCR-1 activity, suggest that assays under zinc-limiting conditions represent a route to phenotypic identification of MCR-1 producing E. coli, and identify key features of the likely catalytic mechanism.
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.