ANTIBIOTICS ENHANCE BINDING OF LIPID A-SPECIFIC MURINE MONOCLONAL-ANTIBODY E5 TO GRAM-NEGATIVE BACTERIA

Cross-protection by anti-lipid A antibodies may be mediated by contrib ution to host defence mechanisms such as enhancement of bactericidal a ctivity and phagocytosis. The lipid A-specific murine monoclonal antib ody (mAb) E5 was evaluated in vitro for its ability to enhance antibac terial effects in concert with antibiotics in order to investigate und erlying mechanisms for the proposed in vivo efficacy. The effect of an tibiotic exposure of several E. coli strains on binding by mAb E5 was examined in solid phase enzyme-linked immunoassay (ELISA) and in compl ement activation and phagocytosis assays. MAb E5 binds scarcely to liv e E. coli, both encapsulated and unencapsulated, but exposure to subin hibitory concentrations of aztreonam and ceftriaxone led to enhanced b inding of mAb E5 compared to mock treated strains. Enhanced binding of mAb E5 to aztreonam-treated E. coli O111:B4 or O7K1 resulted in a mod est increase in complement consumption but complement-mediated phagocy tosis by human polymorphonuclear leukocytes (PMN) of these complexes w as not affected. It was concluded that exposure of E. coli to antibiot ics induced specific alterations in the bacteria, resulting in accessi bility of epitopes recognized by mAb E5. Enhanced binding was found to support complement-mediated host defense mechanisms and might contrib ute to better protection in a joint action of antibiotics and antibodi es.