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A two-tier model of polymyxin B resistance in Burkholderia cenocepacia

Slade A Loutet1, Lauren E Mussen, Ronald S Flannagan

  • 1Centre for Human Immunology, Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada N6A 5C1 Department of Medicine, University of Western Ontario, London, ON, Canada N6A 5C1.

Environmental Microbiology Reports
|June 14, 2013
PubMed

Insights

Burkholderia cenocepacia exhibits high resistance to polymyxin B (PmB) through a two-tier system. Lipopolysaccharide and outer membrane integrity form the primary defense, with additional proteins aiding resistance when the outer membrane is compromised.

Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Antimicrobial Resistance

Background:

  • Burkholderia cenocepacia is an opportunistic pathogen known for extreme antibiotic resistance.
  • Antimicrobial peptide resistance, particularly to polymyxin B (PmB), is a significant challenge.
  • Outer membrane impermeability, mediated by lipopolysaccharide (LPS), is a key factor in intrinsic resistance.

Purpose of the Study:

  • To investigate a hypothesized two-tier model of PmB resistance in B. cenocepacia.
  • To identify specific resistance mechanisms beyond LPS and outer membrane permeability.
  • To understand the contribution of secondary resistance factors when the primary barrier is compromised.

Main Methods:

  • Comparative analysis of gene mutations in isogenic B. cenocepacia strains with full-length LPS and heptoseless LPS.
  • Assessment of proteins involved in PmB resistance in strains with compromised outer membrane permeability.
  • Evaluation of PmB binding and cell permeabilization assays.

Main Results:

  • Identified specific proteins crucial for PmB resistance exclusively in the heptoseless LPS strain.
  • These proteins do not influence initial PmB binding or outer membrane permeabilization.
  • Evidence supports a multi-layered resistance strategy in B. cenocepacia.

Conclusions:

  • B. cenocepacia employs a two-tier resistance mechanism against polymyxin B.
  • The first tier involves LPS and outer membrane barrier function for high-level resistance.
  • A second tier of protein-mediated resistance is activated when the outer membrane permeability is compromised.

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