Polymyxin
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Polymyxins are antibiotics, with a general structure 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 the Gram-positive bacterium Bacillus polymyxa and are selectively toxic for Gram-negative bacteria due to their specificity for lipopolysaccharide in the outer membrane of the cell wall of these organisms.
Polymyxins B and E (also known as colistin) are used in the treatment of infections with gram-negative bacteria.
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[edit] Mode of action
After binding to lipopolysaccharide (LPS) in the outer membrane of Gram-negative bacteria, polymyxins disrupt both the outer and inner membrane. 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 does no longer kill the bacterial cell. However, it still detectably increases the permeability of the bacterial cell wall to other antibiotics, indicating that 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.
[edit] Clinical use
Polymyxin antibiotics are considered relatively neurotoxic and nephrotoxic and, though effective, are therefore used only if less toxic antibiotics cannot. Typical use cases are infections with strains of Pseudomonas aeruginosa or Enterobacteriaceae species that are highly resistant to other types of antibiotics such as cephalosporins.
Polymyxins are not absorbed from the gastrointestinal tract and therefore have to be applied intravenously.
[edit] Use in biomedical research
Polymyxins are used to neutralize or absorb LPS contaminating samples that are 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.
[edit] See also
[edit] References
Tran AX, Lester ME, Stead CM, Raetz CR, Maskell DJ, McGrath SC, Cotter RJ, Trent MS. (2005). "Resistance to the antimicrobial peptide polymyxin requires myristoylation of Escherichia coli and Salmonella typhimurium lipid A.". J. Biol. Chem. 280: 28186-94. doi:. PMID 15951433.
Dixon R.A., Chopra I. (1986). "Polymyxin B and polymyxin B nonapeptide alter cytoplasmic membrane permeability in Escherichia coli.". J. Antimicrob. Chemother. 5: 557-563. PMID 3027012.
Falagas ME, Kasiakou SK (2006). "Toxicity of polymyxins: a systematic review of the evidence from old and recent studies". Crit Care 10 (1): R27. doi:. PMID 16507149.
[edit] External links
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