mcr-9, an Inducible Gene Encoding an Acquired Phosphoethanolamine Transferase in Escherichia coli, and Its Origin

Area of Science:

• Microbiology
• Genetics
• Molecular Biology

Background:

• The plasmid-encoded mcr-9 gene, identified in a colistin-resistant Escherichia coli strain, encodes a putative phosphoethanolamine transferase.
• MCR-9 protein shares homology with other MCR-type enzymes (MCR-1 to -8) conferring polymyxin resistance in Enterobacteriaceae.
• Polymyxins, like colistin, are critical last-resort antibiotics against multidrug-resistant Gram-negative bacteria.

Purpose of the Study:

• To characterize the novel mcr-9 gene and its role in colistin resistance.
• To investigate the mechanism of mcr-9 gene expression and regulation.
• To explore the origin and dissemination of mcr-9.

Main Methods:

• Identification and cloning of the mcr-9 gene from a human fecal Escherichia coli isolate.
• Analysis of lipopolysaccharide modification in MCR-9-producing strains.
• Gene expression studies under varying colistin concentrations and genetic analysis of regulatory systems (qseC, qseB) and plasmid context (IncHI2).

Main Results:

• MCR-9 modifies lipopolysaccharide similarly to MCR-1, but shows a minor impact on polymyxin susceptibility upon initial cloning.
• Subinhibitory colistin concentrations induce mcr-9 gene expression, increasing Minimum Inhibitory Concentrations (MICs).
• Inducible expression is regulated by the downstream two-component system encoded by qseC and qseB, with the gene located on an IncHI2 plasmid.

Conclusions:

• The mcr-9 gene confers inducible colistin resistance in E. coli, mediated by the QseBC regulatory system.
• Silent circulation of mcr genes is possible, requiring specific conditions (e.g., colistin induction) for detection.
• Discovery of mcr-9 on an IncHI2 plasmid highlights potential for horizontal gene transfer and spread of polymyxin resistance.