In vitro and in vivo effect of immunoglobulin G on the integrity of bacterial membranes.
The interaction between a modified 7S immunoglobulin (MISG) and bacterial membranes was studied by adopting in vitro as well as in vivo techniques. Preincubation of Escherichia coli and Pseudomonas aeruginosa with MISG resulted in a release of enzymatic markers from the periplasmic space, whereas no cytoplasmic or membrane-bound enzymes were liberated. Due to the interaction of MISG with the outer membrane of gram-negative rods, the bacteria became more susceptible to the antibacterial action of poorly penetrating penicillins because of a significantly increased rate of uptake. These in vitro effects were corroborated under in vivo conditions by adopting the granuloma pouch model. A single intravenous injection of MISG enhanced the therapeutic efficacy of mezlocillin against E. coli; similarly, the antibacterial activity of penicillin G, oxacillin, cephalothin and cefamandole against Staphylococcus aureus was augmented by MISG. These in vivo effects of MISG were not due to an increased rate of phagocytosis or complement activity. Thus, MISG sensitized bacteria to several beta-lactam antibiotics by disorganizing their outer membrane.
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects*; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology; D016756:Immunoglobulins, Intravenous; D008563:Membrane Lipids / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects*; D001618:beta-Lactamases / Q000378:metabolism; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D008563:Membrane Lipids; D047090:beta-Lactams; D001618:beta-Lactamases