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An image-based assay for high throughput screening of Giardia lamblia
Authors:Gut Jiri  Ang Kenny K H  Legac Jennifer  Arkin Michelle R  Rosenthal Philip J  McKerrow James H
Affiliation:
  • a Sandler Center for Drug Discovery, University of California, San Francisco, USA
  • b Small Molecule Discovery Center and Dept. of Pharmaceutical Chemistry, University of California, San Francisco, USA
  • c School of Medicine, Division of Infectious Diseases, University of California, San Francisco, USA
  • Abstract:
    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.
    Keywords:Giardia lamblia   In vitro cultivation   Inhibitor   High content analysis   High throughput screening
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