An outer membrane-disorganizing peptide PMBN sensitizes E. coli strains to serum bactericidal action.
The small cationic outer membrane-disorganizing peptide PMBN sensitized four smooth, encapsulated strains of Escherichia coli (serotypes 02:K1, 04:K12, 018:K1, and 018:K5) to the lethal action of serum. The concentrations of PMBN required were low (0.3 to 1.0 microgram/ml). One E. coli strain (IH 11030; 075:K5) remained virtually resistant to serum and also to anti-075 hyperimmune serum plus complement (C) even in the presence of PMBN. This strain was nevertheless sensitive to the outer membrane permeability-increasing action of PMBN. In the bactericidal system, PMBN could be replaced by high concentrations of lysine20 or protamine but not lysine4. The PMBN-dependent bactericidal activity of GPS was abolished by heating or zymosan treatment that inactivate its C but not by lack of the action of the classical pathway of the C in C4-deficient GPS. PMBN formed a bactericidal system also with normal rabbit, rat, and human serum but not with mouse serum. The bactericidal system against E. coli 018:K1 and its derivative EH 817 (018:K1-) was found to require a factor that can be removed from normal sera by absorption with a rough E. coli strain. This factor could be replaced by specific anti-018 antibodies. The bactericidal activity of fetal calf serum plus PMBN against E. coli 018:K1 was enhanced by normal rabbit or anti-E. coli 018 hyperimmune serum. We suggest that PMBN unshields the deep structures and the hydrophobic membrane milieu of the outer membrane and facilitates the insertion of the membrane attack complex of the C into this milieu.
D000818:Animals; D000907:Antibodies, Bacterial / Q000502:physiology; D023181:Antimicrobial Cationic Peptides; D001770:Blood Bactericidal Activity / Q000187:drug effects; D001798:Blood Proteins / Q000494:pharmacology*; D003167:Complement Activation; D004926:Escherichia coli / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D006168:Guinea Pigs; D006358:Hot Temperature; D006801:Humans; D008239:Lysine / Q000494:pharmacology; D008565:Membrane Proteins; D051379:Mice; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides / Q000494:pharmacology; D011112:Polymyxin B / Q000031:analogs & derivatives / Q000494:pharmacology*; D011113:Polymyxins / Q000494:pharmacology*; D011479:Protamines / Q000494:pharmacology; D011817:Rabbits; D051381:Rats
D000907:Antibodies, Bacterial; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D008565:Membrane Proteins; D009842:Oligopeptides; D011113:Polymyxins; D011479:Protamines; C021623:bactericidal permeability increasing protein; C038934:polymyxin B nonapeptide; D011112:Polymyxin B; D008239:Lysine