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

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...

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Main Authors: Sonali Eknath Bhalerao, Himanshu Sen, Saumya Raychaudhuri
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0315052
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author Sonali Eknath Bhalerao
Himanshu Sen
Saumya Raychaudhuri
author_facet Sonali Eknath Bhalerao
Himanshu Sen
Saumya Raychaudhuri
author_sort Sonali Eknath Bhalerao
collection DOAJ
description 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.
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spelling doaj-art-6e30bf852fa44d53bd67be95714653872025-08-20T02:21:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-011912e031505210.1371/journal.pone.0315052Administration of novobiocin and apomorphine mitigates cholera toxin mediated cellular toxicity: Lessons from cholera toxin yeast model system.Sonali Eknath BhaleraoHimanshu SenSaumya RaychaudhuriCholera 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.https://doi.org/10.1371/journal.pone.0315052
spellingShingle Sonali Eknath Bhalerao
Himanshu Sen
Saumya Raychaudhuri
Administration of novobiocin and apomorphine mitigates cholera toxin mediated cellular toxicity: Lessons from cholera toxin yeast model system.
PLoS ONE
title Administration of novobiocin and apomorphine mitigates cholera toxin mediated cellular toxicity: Lessons from cholera toxin yeast model system.
title_full Administration of novobiocin and apomorphine mitigates cholera toxin mediated cellular toxicity: Lessons from cholera toxin yeast model system.
title_fullStr Administration of novobiocin and apomorphine mitigates cholera toxin mediated cellular toxicity: Lessons from cholera toxin yeast model system.
title_full_unstemmed Administration of novobiocin and apomorphine mitigates cholera toxin mediated cellular toxicity: Lessons from cholera toxin yeast model system.
title_short Administration of novobiocin and apomorphine mitigates cholera toxin mediated cellular toxicity: Lessons from cholera toxin yeast model system.
title_sort administration of novobiocin and apomorphine mitigates cholera toxin mediated cellular toxicity lessons from cholera toxin yeast model system
url https://doi.org/10.1371/journal.pone.0315052
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