Proceedings of the National Academy of Sciences · 1991 · 580 citations · 23 references
Life SciencesInfectious DiseasesMicrobiologyMedical MicrobiologyMicrobial PathogenesisVaccinologyBacterial ToxinsBacterial Virulence FactorsInfectious DiarrheaMicrobial Virulence FactorsPathogen Virulence FactorsToxin ProductionBacterial Toxin BiologyHeat-labile EnterotoxinIntestinal Mucosa BarrierPathogenesis Of Bacterial ToxinsToxin GenesVirulence Factor ExpressionVirulence Factor ToxinsZonula Occludens Proteins
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.
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Biochemical Education · 1990 · 887 citations
Route of Passive Ion Permeation in Epithelia
E. Frömter, Jared M. Diamond · Nature New Biology · 1972 · 769 citations
Cholera toxin genes: nucleotide sequence, deletion analysis and vaccine development
John J. Mekalanos, Gregory D. Pearson, Nigel Harford et al. · Nature · 1983 · 638 citations · Full text
Gail Hecht, C Pothoulakis, J. Thomas LaMont et al. · Journal of Clinical Investigation · 1988 · 392 citations · Full text