title: Antibiotics enhance binding of lipid A-specific murine monoclonal antibody E5 to Gram-negative bacteria.
abstract: Cross-protection by anti-lipid A antibodies may be mediated by contribution to host defence mechanisms such as enhancement of bactericidal activity and phagocytosis. The lipid A-specific murine monoclonal antibody (mAb) E5 was evaluated in vitro for its ability to enhance antibacterial effects in concert with antibiotics in order to investigate underlying mechanisms for the proposed in vivo efficacy. The effect of antibiotic exposure of several E. coli strains on binding by mAb E5 was examined in solid phase enzyme-linked immunoassay (ELISA) and in complement activation and phagocytosis assays. MAb E5 binds scarcely to live E. coli, both encapsulated and unencapsulated, but exposure to subinhibitory concentrations of aztreonam and ceftriaxone led to enhanced binding 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 modest increase in complement consumption but complement-mediated phagocytosis by human polymorphonuclear leukocytes (PMN) of these complexes was not affected. It was concluded that exposure of E. coli to antibiotics induced specific alterations in the bacteria, resulting in accessbility of epitopes recognized by mAb E5. Enhanced binding was found to support complement-mediated host defense mechanisms and might contribute to better protection in a joint action of antibiotics and antibodies.
authors.affiliation: Eijkman Winkler Institute for Medical Microbiology/U-Gene Research, G04.515, P.O. Box 85500, 3508 GA Utrecht, Netherlands.
authors.forename: A S
authors.initials: AS
authors.lastname: Bouter
authors.forename: K P
authors.initials: KP
authors.lastname: van Kessel
authors.forename: J J
authors.initials: JJ
authors.lastname: Cornelissen
authors.forename: J F
authors.initials: JF
authors.lastname: Schellekens
authors.forename: Y Y
authors.initials: YY
authors.lastname: van der Hoek
authors.forename: H
authors.initials: H
authors.lastname: Snippe
authors.forename: J
authors.initials: J
authors.lastname: Verhoef