878 Bactericidal Activity Of

Bactericidal antibody is required for direct complement-mediated killing of most pathogenic gram-negative bacteria. Although it has been implicitly assumed that bactericidal antibody functions by increasing complement activation and deposition on the bacterial surface, this assumption may not be valid. We have shown previously (1) that bactericidal IgG increases the bactericidal efficiency of C5b-9 for the serum-resistant Escherichia coli 0111 strain 12015, without increasing the extent of C5b-9 deposition. Bactericidal IgG markedly increased the percentage of the total C5b-9 bound to E. coli 011 1 that was inserted into the outer membrane in a saltand protease-resistant form (2). The effect of IgG was mediated at a step before C5 convertase formation since the addition of IgG after the C5 convertase was formed, but before the C5b-9 was deposited, did not kill bacteria (3). These experiments suggested that bactericidal IgG was changing either the location of complement activation or the molecular conformation of C5b-9 on the bacterial surface. We have now extended these studies by showing that (a) nearly one-fifth of the total C3 that is bound in the presence of antibacterial IgG binds covalently to the antibody molecule and (b) complexes of C3b-IgG are threeto fourfold more effective than IgG in presensitizing strain 12015 for complement-mediated killing. Formation of C3b-IgG complexes may be critical for effective killing of some gram-negative bacteria by the serum-complement system.