ArticlePLoS biology2023
A new variant of the colistin resistance gene MCR-1 with co-resistance to β-lactam antibiotics reveals a potential novel antimicrobial peptide.
Article in PLoS biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Fitness costs of mobilised colistin resistance gene 3 (mcr-3): systematic review, epidemiological study, and functional analysis.EBioMedicine · 2025Pooled it
- Structure-based design of subtype-selective psychedelic analogs.Nature communications · 2026Article
- First report of the mcr-1 gene in colistin-resistant Klebsiella pneumoniae in a tertiary care hospital in Tunisia.BMC infectious diseases · 2026Article
- Reviving Old Antibiotics: New Indications and Therapeutic Perspectives-A Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Asymmetric volume-mediated buffer control overcomes sensitivity limits in one-pot RAA-CRISPR/Cas12a visual detection.Analytical and bioanalytical chemistry · 2025Article
- Article
- 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
- Sequence variation in the active site of mobile colistin resistance proteins is evolutionarily accommodated through inter-domain interactions.The Biochemical journal · 2024Article
- Efficient RNA interference method by feeding in Brachionus plicatilis (Rotifera).Biotechnology letters · 2024Article
- Specific glycine-dependent enzyme motion determines the potency of conformation selective inhibitors of threonyl-tRNA synthetase.Communications biology · 2024Article
- Investigation of Plasmid-Mediated Colistin Resistance Genes (mcr-1-8) in Enterobacterales Isolates.Cureus · 2024Article
- Outer membrane permeability of mcr-positive bacteria reveals potent synergy of colistin and macromolecular antibiotics against colistin-resistantFrontiers in microbiology · 2024Article
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The emerging and global spread of a novel plasmid-mediated colistin resistance gene, mcr-1, threatens human health. Expression of the MCR-1 protein affects bacterial fitness and this cost correlates with lipid A perturbation. However, the exact molecular mechanism remains unclear. Here, we identified the MCR-1 M6 variant carrying two-point mutations that conferred co-resistance to β-lactam antibiotics. Compared to wild-type (WT) MCR-1, this variant caused severe disturbance in lipid A, resulting in up-regulation of L, D-transpeptidases (LDTs) pathway, which explains co-resistance to β-lactams. Moreover, we show that a lipid A loading pocket is localized at the linker domain of MCR-1 where these 2 mutations are located. This pocket governs colistin resistance and bacterial membrane permeability, and the mutated pocket in M6 enhances the binding affinity towards lipid A. Based on this new information, we also designed synthetic peptides derived from M6 that exhibit broad-spectrum antimicrobial activity, exposing a potential vulnerability that could be exploited for future antimicrobial drug design.
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