Structure: Warning: the sequence is a close mimic of the natural peptide antibiotic. In the natural form, there are multiple Dab (2,4-diaminobutanoic acid), which are represented here as lysines. The molecule is cyclic due to the formation of an amide bond between the amino group of Dab in position 4 and the carboxyl group of the C-terminus. Residue Leu6 is a D-amino acid and the N-terminus is attached by a fatty acid (Polymyxin E1= colistin A: fatty acid A=6-methyloctanoic acid; Polymyxin E2=colistin B: fatty acid B=6-methylheptanoic acid).
Activity: It preferentially binds to LPS of Gram-negative bacteria and disrupts membranes (Moser et al., 2014). Because of such interesting properties, there is interest in developing polymyxin analogs.
AMPs in use: Colistin sulfate: for oral and topical use. Sodium colistimethate (CMS): for parenteral and inhalation routes. CMS is a prodrug which converts to colistin in vivo. It is less potent and less toxic. Colistin, used alone or in combination, is important to treat Gram-negative infections such as CF involving P. aeruginosa. Polymyxins also promote the release of histamine and serve as safe mucosal adjuvants that enhance vaccine-induced antigen-specific immune responses (for example ovalbumin intranasally immunized mice; Yoshino N et al., 2013).
Toxicity: nephrotoxicity and neurotoxicity.
Updated 1/2014; 8/2015; 11/2015; 4/2017; 12/2017; 2/2020 GW.