Polymyxin B (R=H is polymyxin B1, R=CH3 is polymyxin B2)

Polymyxins are antibiotics,[1] with a general structure consisting of a cyclic peptide with a long hydrophobic tail. They disrupt the structure of the bacterial cell membrane by interacting with its phospholipids. They are produced by nonribosomal peptide synthetase systems in Gram-positive bacteria such as Paenibacillus polymyxa[2] and are selectively toxic for Gram-negative bacteria due to their specificity for the lipopolysaccharide molecule that exists within many Gram-negative outer membranes.

Polymyxins B and E (also known as colistin) are used in the treatment of Gram-negative bacterial infections. The global problem of advancing antimicrobial resistance has led to a renewed interest in their use recently.[3]

Polymyxin M is also known as "mattacin".[4]


  • Clinical use 1
  • Mechanism of action 2
  • Use in biomedical research 3
  • See also 4
  • References 5
  • Further reading 6

Clinical use

Polymyxin antibiotics are relatively neurotoxic and nephrotoxic,[5] so are usually used only as a last resort if modern antibiotics are ineffective or are contraindicated. Typical uses are for infections caused by strains of multiple drug-resistant Pseudomonas aeruginosa or carbapenemase-producing Enterobacteriaceae.

Polymyxins are not absorbed from the gastrointestinal tract, so another route of administration must be chosen, e.g., parenteral (often intravenously) or by inhalation (unless perhaps the targets are bacteria in the gastrointestinal tract). They are also used externally as a cream or drops to treat otitis externa (swimmers ear).[6] Polymixin B is a component of triple antibiotic ointment.

Polymyxins have less effect on trimethoprim/polymyxin) to broaden the effective spectrum.

Mechanism of action

After binding to lipopolysaccharide (LPS) in the outer membrane of Gram-negative bacteria, polymyxins disrupt both the outer and inner membranes. The hydrophobic tail is important in causing membrane damage, suggesting a detergent-like mode of action.

Removal of the hydrophobic tail of polymyxin B yields polymyxin nonapeptide, which still binds to LPS, but no longer kills the bacterial cell. However, it still detectably increases the permeability of the bacterial cell wall to other antibiotics, indicating it still causes some degree of membrane disorganization.

Gram-negative bacteria can develop resistance to polymyxins through various modifications of the LPS structure that inhibit the binding of polymyxins to LPS.[7]

Use in biomedical research

Polymyxins are used to neutralize or absorb LPS, which contaminates samples intended for use in, e.g., immunological experiments. Minimization of LPS contamination can be important because LPS can evoke strong reactions from immune cells and, therefore, distort experimental results.

By increasing permeability of the bacterial membrane system, polymyxin is also used in clinical work to increase release of secreted toxins, such as Shiga toxin from Escherichia coli.[8]

See also


  1. ^ Dixon RA, Chopra I (November 1986). "Polymyxin B and polymyxin B nonapeptide alter cytoplasmic membrane permeability in Escherichia coli". J. Antimicrob. Chemother. 18 (5): 557–563.  
  2. ^ Polymyxins at the US National Library of Medicine Medical Subject Headings (MeSH)
  3. ^ Falagas ME, Grammatikos AP, Michalopoulos A. Potential of old-generation antibiotics to address current need for new antibiotics. Expert Rev Anti Infect Ther. 2008; 6(5):593-600 PMID 18847400
  4. ^ Martin NI, Hu H, Moake MM, et al. (April 2003). "Isolation, structural characterization, and properties of mattacin (polymyxin M), a cyclic peptide antibiotic produced by Paenibacillus kobensis M". J. Biol. Chem. 278 (15): 13124–13132.  
  5. ^ Falagas ME, Kasiakou SK (February 2006). "Toxicity of polymyxins: a systematic review of the evidence from old and recent studies". Crit Care 10 (1): R27.  
  6. ^ Staff, Medicine.net. Last reviewed 16 April 2014 Neomycin/polymyxin/hydrocortisone suspension - otic, Cortisporin, Pediotic
  7. ^ Tran AX, Lester ME, Stead CM, et al. (August 2005). "Resistance to the antimicrobial peptide polymyxin requires myristoylation of Escherichia coli and Salmonella typhimurium lipid A". J. Biol. Chem. 280 (31): 28186–28194.  
  8. ^ Yokoyama et al. 2000. FEMS Microbiol. Lett. 192:139-144.

Further reading

  • Giuliani A, Pirri G, Nicoletto S (2007). "Antimicrobial peptides: an overview of a promising class of therapeutics". Cent. Eur. J. Biol. 2 (1): 1–33.  
  • Pirri G, Giuliani A, Nicoletto S, Pizutto L, Rinaldi A (2009). "Lipopeptides as anti-infectives: a practical perspective". Cent. Eur. J. Biol. 4 (3): 258–273.