Polymyxin

Polymyxins are antibiotics,cite journal |author=Dixon RA, Chopra I |title=Polymyxin B and polymyxin B nonapeptide alter cytoplasmic membrane permeability in Escherichia coli |journal=J. Antimicrob. Chemother. |volume=18 |issue=5 |pages=557–63 |year=1986 |month=November |pmid=3027012 |doi= |url=http://jac.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=3027012] with a general structure consisting of a cyclic
peptide with a long hydrophobic tail. They disrupt the structure of thebacterial cell membrane by interacting with its phospholipids. They areproduced by the Gram-positive bacterium "Bacillus polymyxa" [MeshName|Polymyxins] and areselectively toxic for Gram-negative bacteria due to their specificity forthe lipopolysaccharide molecule that exists within many Gram-negative outer membranes.

Polymyxins B and E (also known as colistin) are used in thetreatment of Gram-negative bacterial infections.

Polymyxin M is also known as "mattacin".cite journal |author=Martin NI, Hu H, Moake MM, "et al" |title=Isolation, structural characterization, and properties of mattacin (polymyxin M), a cyclic peptide antibiotic produced by Paenibacillus kobensis M |journal=J. Biol. Chem. |volume=278 |issue=15 |pages=13124–32 |year=2003 |month=April |pmid=12569104 |doi=10.1074/jbc.M212364200 |url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=12569104]

Mode of action

After binding to lipopolysaccharide (LPS) in the outer membrane of Gram-negativebacteria, polymyxins disrupt both the outer and inner membranes. The hydrophobictail is important in causing membrane damage, suggesting a detergent-likemode 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, itstill detectably increases the permeability of the bacterial cell wall to otherantibiotics, indicating that it still causes some degree of membranedisorganization.

Gram-negative bacteria can develop resistance to polymyxins through variousmodifications of the LPS structure that inhibit the binding of polymyxins toLPS.cite journal |author=Tran AX, Lester ME, Stead CM, "et al" |title=Resistance to the antimicrobial peptide polymyxin requires myristoylation of Escherichia coli and Salmonella typhimurium lipid A |journal=J. Biol. Chem. |volume=280 |issue=31 |pages=28186–94 |year=2005 |month=August |pmid=15951433 |doi=10.1074/jbc.M505020200 |url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=15951433]

Clinical use

Polymyxin antibiotics are considered relatively neurotoxic and nephrotoxiccite journal |author=Falagas ME, Kasiakou SK |title=Toxicity of polymyxins: a systematic review of the evidence from old and recent studies |journal=Crit Care |volume=10 |issue=1 |pages=R27 |year=2006 |month=February |pmid=16507149 |pmc=1550802 |doi=10.1186/cc3995 |url=http://ccforum.com/content/10/1/R27] and, though effective, are therefore used only if less toxic antibiotics are ineffective or are contraindicated. 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 must be administered intravenously.

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.

See also

* Polysporin

References