Structural Modification of Lipopolysaccharide Conferred by mcr-1 in Gram-Negative ESKAPE Pathogens

Yi-Yun Liu1,2, Courtney E Chandler3, Lisa M Leung3

  • 1Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

Insights

The mcr-1 gene confers colistin resistance in key Gram-negative pathogens like E. coli and K. pneumoniae by altering lipid A structures. This necessitates enhanced surveillance for tracking resistance gene spread.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Antimicrobial Resistance

Background:

  • The mcr-1 gene, encoding a phosphoethanolamine transferase, is the first identified plasmid-mediated colistin resistance gene.
  • It has been detected globally in Enterobacteriaceae, posing a significant threat to public health.
  • Colistin is a critical last-resort antibiotic for treating infections caused by multidrug-resistant Gram-negative bacteria.

Purpose of the Study:

  • To investigate the impact of mcr-1 on colistin susceptibility in ESKAPE pathogens.
  • To analyze the structural modifications of lipopolysaccharide (LPS) in response to mcr-1 expression.
  • To assess the risk of colistin resistance mediated by mcr-1 in clinically relevant bacteria.

Main Methods:

  • Minimum Inhibitory Concentration (MIC) assays were performed on laboratory and clinical strains of Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa.
  • Lipid A structures were analyzed using mass spectrometry to detect modifications induced by MCR-1.
  • The presence and effects of mcr-1 were evaluated across different Gram-negative ESKAPE pathogens.

Main Results:

  • Introduction of mcr-1 resulted in significant colistin resistance in E. coli, K. pneumoniae, and A. baumannii.
  • A moderate reduction in colistin susceptibility was observed in P. aeruginosa.
  • Consistent phosphoethanolamine modification of lipid A was detected in all tested species, regardless of the degree of resistance.

Conclusions:

  • mcr-1 expression poses a substantial risk for colistin resistance development in ESKAPE pathogens, particularly K. pneumoniae and A. baumannii.
  • Lipid A modification by MCR-1 can occur even with modest increases in colistin MICs.
  • Advanced surveillance strategies are crucial for monitoring the dissemination of mcr-1 and similar resistance mechanisms.

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