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Citation
Guichard, A., Cruz-Moreno, B.C., Aguilar, B., van Sorge, N.M., Kuang, J., Kurkciyan, A.A., Wang, Z., Hang, S., Pineton de Chambrun, G.P., McCole, D.F., Watnick, P., Nizet, V., Bier, E. (2013). Cholera toxin disrupts barrier function by inhibiting exocyst-mediated trafficking of host proteins to intestinal cell junctions.  Cell Host Microbe 14(3): 294--305.
FlyBase ID
FBrf0222661
Publication Type
Research paper
Abstract
Cholera toxin (CT), a virulence factor elaborated by Vibrio cholerae, is sufficient to induce the severe diarrhea characteristic of cholera. The enzymatic moiety of CT (CtxA) increases cAMP synthesis in intestinal epithelial cells, leading to chloride ion (Cl(-)) efflux through the CFTR Cl(-) channel. To preserve electroneutrality and osmotic balance, sodium ions and water also flow into the intestinal lumen via a paracellular route. We find that CtxA-driven cAMP increase also inhibits Rab11/exocyst-mediated trafficking of host proteins including E-cadherin and Notch signaling components to cell-cell junctions in Drosophila, human intestinal epithelial cells, and ligated mouse ileal loops, thereby disrupting barrier function. Additionally, CtxA induces junctional damage, weight loss, and dye leakage in the Drosophila gut, contributing to lethality from live V. cholerae infection, all of which can be rescued by Rab11 overexpression. These barrier-disrupting effects of CtxA may act in parallel with Cl(-) secretion to drive the pathophysiology of cholera.
Graphical Abstract
Obtained with permission from Cell Press.
PubMed ID
PubMed Central ID
PMC3786442 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cell Host Microbe
    Title
    Cell Host & Microbe
    Publication Year
    2007--
    ISBN/ISSN
    1931-3128 1934-6069
    Data From Reference
    Alleles (12)
    Genes (14)
    Human Disease Models (1)
    Natural transposons (1)
    Insertions (2)
    Experimental Tools (1)
    Transgenic Constructs (5)