Novel polymyxin resistance gene family mcr-12 from environmental Pigmentiphaga litoralis

Area of Science:

• Microbiology
• Environmental Science
• Genetics

Background:

• Mobile colistin resistance (mcr) genes pose a significant threat to treating multidrug-resistant bacterial infections.
• Polymyxins are last-resort antibiotics, making the spread of mcr genes a critical public health concern.
• Environmental reservoirs are increasingly recognized as sources for clinically relevant antimicrobial resistance genes.

Purpose of the Study:

• To identify and characterize a novel mobile colistin resistance gene from an environmental source.
• To evaluate the potential of this new gene to confer resistance in clinically relevant bacterial pathogens.
• To assess the implications of environmental mcr genes for antimicrobial resistance surveillance and One Health initiatives.

Main Methods:

• Isolation and identification of the novel mcr-12 gene from Pigmentiphaga litoralis in Australian sediment.
• Plasmid analysis to determine gene location and co-occurrence with other resistance determinants.
• Functional characterization of mcr-12 through gene expression in susceptible bacterial hosts.
• Biochemical analysis of MCR-12's mechanism of action on lipid A.

Main Results:

• A novel mcr gene, mcr-12, was identified in Pigmentiphaga litoralis, located on plasmid pPLE30.2 alongside a novel beta-lactamase gene.
• Plasmid removal significantly increased polymyxin susceptibility, which was restored upon mcr-12 reintroduction.
• MCR-12 confers polymyxin resistance via phosphoethanolamine transfer to lipid A, despite low amino acid similarity to other MCRs.
• Expression of mcr-12 in Pseudomonas spp. and Acinetobacter baumannii conferred polymyxin resistance, indicating inter-species compatibility.

Conclusions:

• The discovery of mcr-12 in an environmental bacterium outside Gammaproteobacteria expands the known diversity of mobile colistin resistance genes.
• mcr-12 can confer polymyxin resistance in clinically relevant pathogens, underscoring the One Health threat posed by environmental resistance reservoirs.
• Enhanced surveillance of environmental bacteria is crucial for detecting and controlling the emergence and spread of novel antimicrobial resistance genes.