A novel in vitro image-based assay identifies new drug leads for giardiasis

• Published in: International journal for parasitology -- drugs and drug resistance 2017-04, Vol.7 (1), p.83-89
• Main Authors: Hart, Christopher J.S., Munro, Taylah, Andrews, Katherine T., Ryan, John H., Riches, Andrew G., Skinner-Adams, Tina S.
• Format: Article
• Language: English
• Subjects: Antiprotozoal Agents - chemistry; Antiprotozoal Agents - isolation & purification; Antiprotozoal Agents - pharmacology; Automation; Drug Discovery; Drug Resistance; Giardia; Giardia lamblia - drug effects; Giardia lamblia - growth & development; Image Processing, Computer-Assisted; Image-based assay; Life Cycle Stages - drug effects; Malaria Box; Parasitic Sensitivity Tests
• ISSN: 2211-3207; 2211-3207
• DOI: 10.1016/j.ijpddr.2017.01.005

Giardia duodenalis is an intestinal parasite that causes giardiasis, a widespread human gastrointestinal disease. Treatment of giardiasis relies on a small arsenal of compounds that can suffer from limitations including side-effects, variable treatment efficacy and parasite drug resistance. Thus new anti-Giardia drug leads are required. The search for new compounds with anti-Giardia activity currently depends on assays that can be labour-intensive, expensive and restricted to measuring activity at a single time-point. Here we describe a new in vitro assay to assess anti-Giardia activity. This image-based assay utilizes the Perkin-Elmer Operetta® and permits automated assessment of parasite growth at multiple time points without cell-staining. Using this new approach, we assessed the “Malaria Box” compound set for anti-Giardia activity. Three compounds with sub-μM activity (IC50 0.6–0.9 μM) were identified as potential starting points for giardiasis drug discovery. [Display omitted] •We describe a new automated image-based method to enumerate Giardia trophozoites.•This method permits the assessment of parasite growth at multiple time points without staining.•The “Malaria Box” compound set was assessed for anti-Giardia activity using this approach.•Three compounds with sub-μM activity were identified.