ArticleEBioMedicine2018
Spread of MCR-3 Colistin Resistance in China: An Epidemiological, Genomic and Mechanistic Study.
Article in EBioMedicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 47 papers, 2 of them syntheses that pooled it.
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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
47 citing papers in PubMed, 2 syntheses or guidelines pooled it, 93 citations in OpenAlex.
- Fitness costs of mobilised colistin resistance gene 3 (mcr-3): systematic review, epidemiological study, and functional analysis.EBioMedicine · 2025Pooled it
- Antibiotic resistance of fecal carriage of Escherichia coli from pig farms in China: a meta-analysis.Environmental science and pollution research international · 2022Pooled it
- Macrophage-mediated antibiotic evasion and competitive dominance of mcr-3-carrying Escherichia coli.PLoS pathogens · 2026Article
- Balanced Expression of the Diiron Oxygenase BioE Is Essential for Biotin Homeostasis in Elizabethkingia meningoseptica.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Article
- Detection and genetic characterisation of ESBL, carbapenemase, and mcr-1 genes in Gram-negative bacterial isolates from companion animals in Batna, Algeria.Antonie van Leeuwenhoek · 2025Article
- DNA Polymerase IV dinB Favors the Adaptive Fitness of mcr-carrying Bacteria Through a Negative Feedback Regulatory Mechanism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- ISiScience · 2025Article
- Review
- Article
- First report of multidrug-resistant carbapenemase-producingMicrobiology spectrum · 2024Article
- Flesh Without Blood: The Public Health Benefits of Lab-Grown Meat.Journal of bioethical inquiry · 2024Article
- Endopeptidase O promotesVirulence · 2023Article
- A Review of Resistance to Polymyxins and Evolving Mobile Colistin Resistance Gene (Antibiotics (Basel, Switzerland) · 2023Review
- Phosphoethanolamine Transferases as Drug Discovery Targets for Therapeutic Treatment of Multi-Drug Resistant Pathogenic Gram-Negative Bacteria.Antibiotics (Basel, Switzerland) · 2023Review
- A Single Residue within the MCR-1 Protein Confers Anticipatory Resilience.Microbiology spectrum · 2023Article
- Antimicrobial Resistant Pathogens Detected in Raw Pork and Poultry Meat in Retailing Outlets in Kenya.Antibiotics (Basel, Switzerland) · 2023Article
- Pyrazolones Potentiate Colistin Activity against MCR-1-Producing Resistant Bacteria: Computational and Microbiological Study.ACS omega · 2023Article
- More thanFrontiers in cellular and infection microbiology · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMobilized resistance to colistin is evolving rapidly and its global dissemination poses a severe threat to human health and safety. Transferable colistin resistance gene, mcr-3, first identified in Shandong, China, has already been found in several countries in multidrug-resistant human infections. Here we track the spread of mcr-3 within 13 provinces in China and provide a complete characterization of its evolution, structure and function.
methodsA total of 6497 non-duplicate samples were collected from thirteen provinces in China, from 2016 to 2017 and then screened for the presence of mcr-3 gene by PCR amplification. mcr-3-positive isolates were analyzed for antibiotic resistance and by southern blot hybridization, transfer analysis and plasmid typing. We then examined the molecular evolution of MCR-3 through phylogenetic analysis. Furthermore, we also characterized the structure and function of MCR-3 through circular dichroism analyses, inductively coupled plasma mass spectrometry (ICP-MS), liquid chromatography mass spectrometry (LC/MS), confocal microscopy and chemical rescue tests.
findings49 samples (49/6497 = 0.75%) were mcr-3 positive, comprising 40 samples (40/4144 = 0.97%) from 2017 and 9 samples (9/2353 = 0.38%) from 2016. Overall, mcr-3-positive isolates were distributed in animals and humans in 8 of the 13 provinces. Three mcr-3-positive IncP-type and one mcr-1-bearing IncHI2-like plasmids were identified and characterized. MCR-3 clusters with PEA transferases from Aeromonas and other bacteria and forms a phylogenetic entity that is distinct from the MCR-1/2/P(M) family, the largest group of transferable colistin resistance determinants. Despite that the two domains of MCR-3 not being exchangeable with their counterparts in MCR-1/2, structure-guided functional mapping of MCR-3 defines a conserved PE-lipid recognizing cavity prerequisite for its enzymatic catalysis and its resultant phenotypic resistance to colistin. We therefore propose that MCR-3 uses a possible "ping-pong" mechanism to transfer the moiety of PEA from its donor PE to the 1(or 4')-phosphate of lipid A via an adduct of MCR-3-bound PEA. Additionally, the expression of MCR-3 in E. coli prevents the colistin-triggered formation of reactive oxygen species (ROS) and interferes bacterial growth and viability.
interpretationOur results provide an evolutionary, structural and functional definition of MCR-3 and its epidemiology in China, paving the way for smarter policies, better surveillance and effective treatments.
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