Neutralization of endotoxin toxicity in chick embryos by antibiotics

Rifkind, David (University of Colorado Medical Center, Denver), and John D. Palmer. Neutralization of endotoxin toxicity in chick embryos by antibiotics. J. Bacteriol. 92:815-819. 1966.-Three cationic cyclic polypeptide antibiotics, polymyxin B sulfate colistin sulfate, and tyrocidine hydrochloride, were shown to neutralize endotoxin lethality in chick embryos. The neutralizing potency of these antibiotics was approximately equivalent, 0.06 to 0.11 mumole of antibiotic per mug of endotoxin. Methane sulfonation of colistin resulted in a 13-fold decrease in endotoxin-neutralizing potency. Other cationic cyclic polypeptide antibiotics were inactive, as well all other classes of antibiotics tested, including the neutral cyclic polypeptides. Several nonantibiotic polycationic proteins and polymers tested were also inactive. It is suggested that certain cationic cyclic polypeptide antibiotics neutralize by combining directly with the toxic moiety of the endotoxin molecule. Possibly this combination involves the cationic groups of the antibiotics and the polyphosphate groups of the phospholipid component of endotoxin.