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Small Molecule Inhibitor Screen Reveals Calcium Channel Signaling as a Mechanistic Mediator of TcdB-Induced Necrosis.

ACS Chem Biol

May 2020

Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, A4116A Medical Center North, 1161 21st Avenue South, Nashville, Tennessee 37232-2363, United States.

is the leading cause of nosocomial diarrhea in the United States. The primary virulence factors are two homologous glucosyltransferase toxins, TcdA and TcdB, that inactivate host Rho-family GTPases. The glucosyltransferase activity has been linked to a "cytopathic" disruption of the actin cytoskeleton and contributes to the disruption of tight junctions and the production of pro-inflammatory cytokines.

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