S1 Data set -

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.霍乱是一种凶险的烈性传染病。这一致命疾病的肆虐至今仍在发展中国家持续存在。尽管目前已有多种治疗策略用于对抗、遏制霍乱，但仍亟需开发安全高效的新型药物以实现对该疾病的有效管控。鉴于上述研究需求，本团队首先成功构建了可诱导表达霍乱毒素A亚基（cholera toxin subunit A）的酵母模型，随后利用该模型针对霍乱毒素A亚基开展小分子化合物库筛选。本研究最终发现了一种小分子化合物——阿扑吗啡（apomorphine，一款帕金森病治疗药物），其可有效降低酵母模型中毒性亚基的致死活性。此外，新生霉素（novobiocin）作为ADP核糖基化（ADP ribosylation）过程的抑制剂——而该过程正是霍乱毒素作用于宿主的关键生化事件——同样被证实可将酵母细胞从霍乱毒素A亚基介导的毒性中拯救出来。最后，本研究在霍乱毒素处理的人肠道上皮细胞系HT29（human gut epithelial cell line HT29）中验证了两种化合物的作用效果，结果显示阿扑吗啡与新生霉素均可阻断霍乱毒素介导的HT29肠道上皮细胞毒性损伤。