Sandler Center for Drug Discovery, University of California, San Francisco, USA.
J Microbiol Methods. 2011 Mar;84(3):398-405. doi: 10.1016/j.mimet.2010.12.026. Epub 2011 Jan 22.
Giardia lamblia is a protozoan parasite that causes widespread gastrointestinal illness. Drugs to treat giardiasis are limited, but efforts to discover new anti-giardial compounds are constrained by the lack of a facile system for cell culture and inhibitor testing. We achieved robust and reproducible growth of G. lamblia in 384-well tissue culture plates in a modified TYI-S-33 medium. A high throughput assay for the screening of potential anti-giardial compounds was developed utilizing the WB strain of G. lamblia and automated optical detection of parasites after growth with tested inhibitors. We screened a library of 1600 known bioactive molecules and identified 12 compounds that inhibited growth of G. lamblia at low- or sub-micromolar concentrations. Our high throughput assay should facilitate evaluation of available chemical libraries for novel drugs to treat giardiasis.
蓝氏贾第鞭毛虫是一种引起广泛胃肠道疾病的原生动物寄生虫。治疗贾第鞭毛虫病的药物有限,但由于缺乏简便的细胞培养和抑制剂测试系统,发现新的抗贾第鞭毛虫化合物的努力受到限制。我们在改良的 TYI-S-33 培养基中在 384 孔组织培养板中实现了蓝氏贾第鞭毛虫的稳健和可重复的生长。利用 WB 株蓝氏贾第鞭毛虫和用测试抑制剂生长后寄生虫的自动光学检测,开发了一种用于筛选潜在抗贾第鞭毛虫化合物的高通量筛选测定法。我们筛选了 1600 种已知生物活性分子的文库,发现 12 种化合物以低或亚微米浓度抑制蓝氏贾第鞭毛虫的生长。我们的高通量测定法应该有助于评估现有的化学文库,以寻找治疗贾第鞭毛虫病的新药。