Vibrio cholerae Produces a Second Enterotoxin, which Affects Intestinal Tight Junctions

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 88; no. 12; pp. 5242 - 5246
• Main Authors: Fasano, Alessio, Baudry, Bernadette, Pumplin, David W., Wasserman, Steven S., Tall, Ben D., Ketley, Julian M.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 15-06-1991; National Acad Sciences
• Subjects: Animals; Bacteriology; Biological and medical sciences; Cholera; Cholera Toxin - biosynthesis; Cholera Toxin - genetics; Cholera Toxin - toxicity; Diarrhea; Enterotoxins - biosynthesis; Enterotoxins - genetics; Enterotoxins - toxicity; Fundamental and applied biological sciences. Psychology; Ileum - ultrastructure; Intercellular Junctions - ultrastructure; Intestinal Mucosa - ultrastructure; Male; Microbiology; Microscopy, Electron; Mutation; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; Rabbits; Sodium; Tight junctions; Tissue culture techniques; Toxins; Transcriptional regulatory elements; Vaccination; Vibrio cholerae; Vibrio cholerae - metabolism; Vibrio cholerae - pathogenicity; Virulence; Volunteerism; Gene product; Toxicity; Vibrio cholerae; Gut; Rabbit; Permeability; Lagomorpha; Inactivation; Electron microscopy; Vertebrata; Mammalia; Enterotoxin; Bacteria; Vibrionaceae; Tight junction; Structure modification; Mutation; Mechanism of action
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.88.12.5242

Attenuated Vibrio cholerae vaccine strains specifically mutated in genes encoding cholera toxin (CT) are still capable of causing mild to moderate diarrhea. Culture supernatants of V. cholerae strains, both CT-positive and CT-negative, were examined in Ussing chambers, and a toxin was found that increases the permeability of the small intestinal mucosa by affecting the structure of the intercellular tight junction, or zonula occludens. The activity of this toxin is reversible, heat-labile, sensitive to protease digestion, and found in culture supernatant fractions containing molecules between 10 and 30 kDa in size. Production of this factor (named ZOT for zonula occludens toxin) correlates with diarrheagenicity of V. cholerae strains in volunteers and may represent another virulence factor of infectious diarrhea that must be eliminated to achieve a safe and effective live oral vaccine against cholera.