Administration of novobiocin and apomorphine mitigates cholera toxin mediated cellular toxicity: Lessons from cholera toxin yeast model system.

Abstract

Cholera is a dreadful disease. The scourge of this deadly disease is still evident in the developing world. Though several therapeutic strategies are in practice to combat and contain the disease, there is still a need for new drugs to control the disease safely and effectively. Keeping in view the concern, we first successfully established an inducible yeast model to express cholera toxin subunit A, and then used this yeast model, to screen a small molecule library against cholera toxin A subunit. Our effort resulted in the discovery of a small molecule, apomorphine (a Parkinson's disease drug) effective in reducing the lethality of toxic subunit in yeast model. In addition, novobiocin, an inhibitor of ADP ribosylation process, a key biochemical event through which cholera toxin exerts its action on host, was also found to rescue yeast cells from cholera toxin A subunit mediated toxicity. Finally, the effects of both molecules were tested on the cholera toxin-treated human gut epithelial cell line HT29, and it was observed that both apomorphine and novobiocin prevented cholera toxin-mediated cellular toxicity on HT29 intestinal epithelial cells.