Structure and Mechanism of Action

The polymyxins are polypeptide antibiotics that contain both hydrophilic and lipophilic regions. These antibiotics accumulate in the cell membrane and probably interact with membrane phospholipids. Most likely the fatty acid portion of the antibiotic penetrates the hy-drophobic portion of the membrane phospholipid and the polypeptide ring binds to the exposed phosphate groups of the membrane. Such an interaction would distort the membrane, impair its selective permeability, produce leakage of metabolites, and inhibit cellular processes. In the laboratory polymyxin B can neutralize the effects of bacterial lipopolysaccharide (LPS) of gram-negative organisms and may stimulate the biosynthesis of complement component C3, factor B, inter-leukin (IL) 6, and granulocyte-macrophage colony stimulating factor (GM-CSF). Its clinical use in gramnegative sepsis has not been established. These antibiotics also are toxic to mammalian cells.

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