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Polymyxins

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  • Polymyxin is an old class of nonribosomal cyclic lipopeptide antibiotics
  • originally discovered in 1947
  • discovered as a metabolite of a soil-dwelling bacterium, Paenibacillus polymyxa subsp. Colistinus

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  • Polymyxins consist of polymyxins A∼E,
  • polymyxin B and polymyxin E (colistin) are currently used
  • A, C and D are highly toxic to humans-damage kidneys
  • Use is limited due tot toxicity and other drugs available

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General Features- (Colistin and Polymyxin B)

  • structure consisting of ring and tail parts.
  • ring is composed of a cyclic polycationic peptide and
  • the tail is made up of an acylated tripeptide chain attached with fatty acids at the N-terminus
  • D-phenylalanine in polymyxin B is replaced by a D-leucine residue in colistin – ring
  • prodrug, namely colistin methanesulfonate (CMS), given IV

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Antibacterial Mechanism of Polymyxins

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Mechanisms of Bacterial Resistance to Polymyxins

  • PhoP-PhoQ Two-Component System

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  • Species-Specific Resistance Mechanisms.

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  • The MexAB-OprM efflux pump in Pseudomonas aeruginosa has been proposed to confer tolerance towards polymyxin E
  • The AcrAB efflux pump encoded by acrAB operon can give Klebsiella pneumoniae resistance to polymyxin B
  • A multidrug efflux pump NorM in Burkholderia vietnamien has been shown to contribute to polymyxin resistance �