ArticleThe Journal of antimicrobial chemotherapy2018
Fitness cost of mcr-1-mediated polymyxin resistance in Klebsiella pneumoniae.
Article in The Journal of antimicrobial chemotherapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 88 citations in OpenAlex.
- Within-host mechanisms of resistance evolution in polymyxin B-resistant Klebsiella pneumoniae without prior exposure.Annals of clinical microbiology and antimicrobials · 2026Article
- Clinical characteristics and molecular evolution of ST11-KL64 carbapenem-resistant hypervirulentMicrobiology spectrum · 2026Article
- A novel ABC family protein participates in the regulation of fitness cost caused byFundamental research · 2026Article
- Molecular Insights into Carbapenem Resistance inInternational journal of molecular sciences · 2026Review
- Host-dependent effects ofFrontiers in microbiology · 2026Article
- Clinical Characteristics and Whole-Genome Sequencing Analysis of Carbapenem- and Colistin-Resistant HypervirulentInfection and drug resistance · 2026Article
- Genetic Characterization of a Linezolid- and Penicillin-ResistantTransboundary and emerging diseases · 2025Article
- ISmBio · 2024Article
- Horizontal gene transfer facilitates the molecular reverse-evolution of antibiotic sensitivity in experimental populations of H. pylori.Nature ecology & evolution · 2024Article
- Polymyxins with Potent Antibacterial Activity against Colistin-Resistant Pathogens: Fine-Tuning Hydrophobicity with Unnatural Amino Acids.Journal of medicinal chemistry · 2024Article
- Structural biology of MCR-1-mediated resistance to polymyxin antibiotics.Current opinion in structural biology · 2023Review
- Lipid A Modification and Metabolic Adaptation in Polymyxin-Resistant, New Delhi Metallo-β-Lactamase-Producing Klebsiella pneumoniae.Microbiology spectrum · 2023Article
- A Single Residue within the MCR-1 Protein Confers Anticipatory Resilience.Microbiology spectrum · 2023Article
- Antimicrobial Resistance in Romania: Updates on Gram-Negative ESCAPE Pathogens in the Clinical, Veterinary, and Aquatic Sectors.International journal of molecular sciences · 2023Review
- MCR-1-dependent lipid remodelling compromises the viability of Gram-negative bacteria.Emerging microbes & infections · 2022Article
- Effect of Different Tolerable Levels of ConstitutiveMicrobiology spectrum · 2022Article
- ISMicrobial genomics · 2022Article
- Transmissibility and Persistence of the Plasmid-Borne Mobile Colistin Resistance Gene,Antibiotics (Basel, Switzerland) · 2022Article
- Longitudinal study of the mcr-1 gene prevalence in Spanish food-producing pigs from 1998 to 2021 and its relationship with the use of polymyxins.Porcine health management · 2022Article
- Polymyxin Resistance in Clinical Isolates ofFrontiers in cellular and infection microbiology · 2022Article
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8 authors at 4 institutions in 1 country.
Funding
Abstract
Objectives: The discovery of mobile colistin resistance mcr-1, a plasmid-borne polymyxin resistance gene, highlights the potential for widespread resistance to the last-line polymyxins. In the present study, we investigated the impact of mcr-1 acquisition on polymyxin resistance and biological fitness in Klebsiella pneumoniae. Methods: K. pneumoniae B5055 was used as the parental strain for the construction of strains carrying vector only (pBBR1MCS-5) and mcr-1 recombinant plasmids (pmcr-1). Plasmid stability was determined by serial passaging for 10 consecutive days in antibiotic-free LB broth, followed by patching on gentamicin-containing and antibiotic-free LB agar plates. Lipid A was analysed using LC-MS. The biological fitness was examined using an in vitro competition assay analysed with flow cytometry. The in vivo fitness cost of mcr-1 was evaluated in a neutropenic mouse thigh infection model. Results: Increased polymyxin resistance was observed following acquisition of mcr-1 in K. pneumoniae B5055. The modification of lipid A with phosphoethanolamine following mcr-1 addition was demonstrated by lipid A profiling. The plasmid stability assay revealed the instability of the plasmid after acquiring mcr-1. Reduced in vitro biological fitness and in vivo growth were observed with the mcr-1-carrying K. pneumoniae strain. Conclusions: Although mcr-1 confers a moderate level of polymyxin resistance, it is associated with a significant biological fitness cost in K. pneumoniae. This indicates that mcr-1-mediated resistance in K. pneumoniae could be attenuated by limiting the usage of polymyxins.
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