Targeting lipopolysaccharides by the nontoxic polymyxin B nonapeptide sensitizes resistant Escherichia coli to the bactericidal effect of human neutrophils

The nonapeptide of polymyxin B (PMBN) has been reported to sensitize variou s pathogenic gram-negative bacteria to the direct bactericidal effect of hu man serum. To investigate the impact of PMBN on human neutrophil-effected k illing of the serum- and phagocytosis-resistant Escherichia coli strains C1 4 and O111, serum was coapplied with PMBN or with neutrophils, but this did not result in decreased numbers of viable bacteria. In contrast, the most potent bacterial killing occurred in the presence of neutrophils plus serum components plus PMBN. The effect of this on E. coli C14 was the appearance of inositol phosphates, diacylglycerol, respiratory burst, elastase libera tion, and generation of lipid mediators (leukotriene B-4, 5-HETE, and plate let-activating factor). Strong neutrophil activation required early, but no t late, complement components and was blocked by inhibition of phagocytosis with cytochalasin D, PMBN seems to cause dramatic support of natural host defense by complement-dependent sensitization of E. coli to the bactericida l efficacy of human neutrophils.