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Effect of polymyxins on the lipopolysaccharide-defective mutants of Proteus mirabilis

W Kaca1, J Radziejewska-Lebrecht, U R Bhat

  • 1Institute of Microbiology, University of Lódź, Poland.

Microbios
|January 1, 1990
PubMed

Insights

Polymyxins B and E effectiveness against Proteus mirabilis varies. A mutant lacking 4-amino-4-deoxy-L-arabinose showed polymyxin sensitivity, unlike resistant strains, suggesting LPS modification impacts susceptibility.

Area of Science:

  • Microbiology
  • Bacterial Genetics
  • Drug Resistance

Background:

  • Polymyxins are critical antibiotics for treating infections caused by Gram-negative bacteria.
  • Proteus mirabilis exhibits variable resistance to polymyxins, complicating treatment strategies.

Purpose of the Study:

  • To investigate the differential susceptibility of Proteus mirabilis strains to polymyxins B and E.
  • To elucidate the role of lipopolysaccharide (LPS) structure in polymyxin resistance.

Main Methods:

  • Comparative analysis of polymyxin B and E effects on smooth and rough Proteus mirabilis strains.
  • Lipopolysaccharide (LPS) binding assays with polymyxin B.
  • Assessment of polymyxin susceptibility following treatment with chemical agents.

Main Results:

  • A P. mirabilis mutant (R4/028) lacking 4-amino-4-deoxy-L-arabinose was sensitive to both polymyxins, while other strains were resistant.
  • LPS from the sensitive mutant bound 50% more polymyxin B compared to LPS from resistant strains.
  • Chemical treatments (iodoacetamide, N-ethylmaleimide, chloramphenicol) restored polymyxin sensitivity in resistant strains.

Conclusions:

  • The absence of 4-amino-4-deoxy-L-arabinose in LPS significantly enhances polymyxin susceptibility in P. mirabilis.
  • LPS structure is a key determinant of polymyxin resistance in Proteus mirabilis.
  • Targeting LPS modification pathways may offer strategies to overcome polymyxin resistance.

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