Pathogenesis of Shigella Diarrhea: Evidence for a Developmentally Regulated Glycolipid Receptor for Shigella Toxin Involved in the Fluid Secretory Response of Rabbit Small Intestine

• Published in: The Journal of infectious diseases Vol. 157; no. 5; pp. 1023 - 1031
• Main Authors: Mobassaleh, Munir, Donohue-Rolfe, Arthur, Jacewicz, Mary, Grand, Richard J., Keusch, Gerald T.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.05.1988; University of Chicago Press
• Subjects: Age; Aging - metabolism; Animals; Bacterial Toxins - metabolism; Bacterial Toxins - pharmacology; Bacteriology; Binding sites; Biological and medical sciences; Chromatography, High Pressure Liquid; Electrophoresis, Polyacrylamide Gel; Fundamental and applied biological sciences. Psychology; Gels; Globosides - metabolism; Glycolipids; Intestine, Small - growth & development; Intestine, Small - metabolism; Microbiology; Microvilli - metabolism; Original Articles; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; Rabbits; Receptors; Receptors, Cell Surface; Receptors, Immunologic - metabolism; Secretion; Shiga Toxins; Shigella; Shigella dysenteriae; Small intestine; Toxins; Trihexosylceramides; Ligand binding; Radiolabelling; Gel electrophoresis; Rabbit; Lagomorpha; Small intestine; Shigellosis; Glycolipid; Infection; Thin layer chromatography; Toxin; Vertebrata; Mammalia; Bacteriosis; Bacteria; Digestive diseases; Membrane; Escherichieae; Shigella; Enterobacteriaceae; Biological receptor
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/157.5.1023

Shigella toxin reproduces the major manifestations of shigellosis in ligated intestinal loops from adult rabbits and binds to a microvillus membrane (MVM) glycolipid receptor, globotriaosylceramide (Gb3). Because neonatal human shigellosis is uncommon, we used the animal model for obtaining MVMs from rabbits of different ages to determine the presence of toxin receptors and Gb3 and to measure the fluid secretory response to toxin in ligated ileal loops. A single class of MVM receptors for 125I-Iabeled shigella toxin, first detected at 20 d of age, reached adult levels by 24 d (n = 1.7−23.8 × 1010/µg of protein; K = 1.1−3.8 × 109 M−1). Binding was specific for toxin subunit B. A toxin binding MVM glycolipid, identified as Gb3, was detected in animals ≥ 16 d of age by high-performance thin-layer chromatography and autoradiography. Fluid secretion in response to shigella toxin in ligated small bowel loops occurred in temporal relation to the appearance of Gb3, a result thus indicating the involvement of Gb3 in mediating the toxin effects.