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Development of a Cytopathic Effect-Based Phenotypic Screening Assay against Cryptosporidium
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2018-01-17 00:00:00 , DOI: 10.1021/acsinfecdis.7b00247 Alexander T. Chao 1, 2 , Boon Heng Lee 1 , Kah Fei Wan 1 , Jeremy Selva 1 , Bin Zou 1 , Peter Gedeck 1 , David John Beer 1 , Thierry T. Diagana 1, 2 , Ghislain M. C. Bonamy 1, 3 , Ujjini H. Manjunatha 1, 2
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2018-01-17 00:00:00 , DOI: 10.1021/acsinfecdis.7b00247 Alexander T. Chao 1, 2 , Boon Heng Lee 1 , Kah Fei Wan 1 , Jeremy Selva 1 , Bin Zou 1 , Peter Gedeck 1 , David John Beer 1 , Thierry T. Diagana 1, 2 , Ghislain M. C. Bonamy 1, 3 , Ujjini H. Manjunatha 1, 2
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Cryptosporidiosis is a diarrheal disease predominantly caused by Cryptosporidium parvum (Cp) and Cryptosporidium hominis (Ch), apicomplexan parasites which infect the intestinal epithelial cells of their human hosts. The only approved drug for cryptosporidiosis is nitazoxanide, which shows limited efficacy in immunocompromised children, the most vulnerable patient population. Thus, new therapeutics and in vitro infection models are urgently needed to address the current unmet medical need. Toward this aim, we have developed novel cytopathic effect (CPE)-based Cp and Ch assays in human colonic tumor (HCT-8) cells and compared them to traditional imaging formats. Further model validation was achieved through screening a collection of FDA-approved drugs and confirming many previously known anti-Cryptosporidium hits as well as identifying a few novel candidates. Collectively, our data reveals this model to be a simple, functional, and homogeneous gain of signal format amenable to high throughput screening, opening new avenues for the discovery of novel anticryptosporidials.
中文翻译：
基于细胞病变效应的针对隐孢子虫的表型筛选试验的建立
隐孢子虫病是由主要引起腹泻疾病微小隐孢子虫（的Cp）和隐孢子虫，人型（章），其感染它们的人类宿主的肠上皮细胞顶复门寄生虫。唯一批准用于治疗隐孢子虫病的药物是硝唑尼特，它在免疫力低下的儿童（最脆弱的患者群体）中显示出有限的功效。因此，迫切需要新的治疗方法和体外感染模型来解决当前未满足的医疗需求。为了实现这一目标，我们开发了基于细胞病变效应（CPE）的新型Cp和Ch检测人类结肠肿瘤（HCT-8）细胞并将其与传统成像格式进行比较。通过筛选一系列FDA批准的药物并确认许多先前已知的抗隐孢子虫命中以及鉴定一些新的候选药物，从而实现了进一步的模型验证。总的来说，我们的数据表明该模型是一种简单，功能均匀的信号格式增益，适用于高通量筛选，为发现新型抗隐孢子虫打开了新途径。
更新日期：2018-01-17
中文翻译：
基于细胞病变效应的针对隐孢子虫的表型筛选试验的建立
隐孢子虫病是由主要引起腹泻疾病微小隐孢子虫（的Cp）和隐孢子虫，人型（章），其感染它们的人类宿主的肠上皮细胞顶复门寄生虫。唯一批准用于治疗隐孢子虫病的药物是硝唑尼特，它在免疫力低下的儿童（最脆弱的患者群体）中显示出有限的功效。因此，迫切需要新的治疗方法和体外感染模型来解决当前未满足的医疗需求。为了实现这一目标，我们开发了基于细胞病变效应（CPE）的新型Cp和Ch检测人类结肠肿瘤（HCT-8）细胞并将其与传统成像格式进行比较。通过筛选一系列FDA批准的药物并确认许多先前已知的抗隐孢子虫命中以及鉴定一些新的候选药物，从而实现了进一步的模型验证。总的来说，我们的数据表明该模型是一种简单，功能均匀的信号格式增益，适用于高通量筛选，为发现新型抗隐孢子虫打开了新途径。
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