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Vibrio cholerae produces a second enterotoxin, which affects intestinal tight junctions
A Fasano1, B Baudry, D W Pumplin
1Department of Medicine, University of Maryland School of Medicine, Baltimore 21201.
Summary
A newly identified zonula occludens toxin (ZOT) from Vibrio cholerae increases intestinal permeability. Eliminating this toxin is crucial for developing safe and effective live oral cholera vaccines.
Area of Science:
- Microbiology
- Gastroenterology
- Vaccinology
Background:
- Attenuated Vibrio cholerae vaccine strains, despite lacking cholera toxin (CT), can still cause diarrhea.
- This suggests the involvement of other virulence factors in V. cholerae-induced diarrheal diseases.
Purpose of the Study:
- To investigate the cause of diarrhea induced by CT-negative V. cholerae strains.
- To identify and characterize novel virulence factors contributing to V. cholerae pathogenicity.
Main Methods:
- Analysis of culture supernatants from both CT-positive and CT-negative V. cholerae strains using Ussing chambers.
- Characterization of the identified toxin's properties, including molecular weight, heat lability, and protease sensitivity.
Main Results:
- A toxin, named zonula occludens toxin (ZOT), was identified in V. cholerae culture supernatants.
- ZOT increases small intestinal mucosal permeability by disrupting intercellular tight junctions (zonula occludens).
- ZOT activity is heat-labile, protease-sensitive, and associated with molecules of 10-30 kDa; its production correlates with diarrheagenicity.
Conclusions:
- Zonula occludens toxin (ZOT) is a novel virulence factor of Vibrio cholerae that contributes to diarrhea.
- The identification and characterization of ZOT are critical for the development of safe and effective live oral cholera vaccines.