A novel in vitro image-based assay identifies new drug leads for giardiasis.
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 (IC500.6-0.9 μM) were identified as potential starting points for giardiasis drug discovery.
Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia.
Christopher J S
CJ
Hart
Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia.
Taylah
T
Munro
Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia.
Katherine T
KT
Andrews
Commonwealth Scientific and Industrial Research Organization, Biomedical Manufacturing, Clayton, Victoria 3168, Australia.
John H
JH
Ryan
Commonwealth Scientific and Industrial Research Organization, Biomedical Manufacturing, Clayton, Victoria 3168, Australia.
Andrew G
AG
Riches
Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia. Electronic address: t.skinner-adams@griffith.edu.au.
Tina S
TS
Skinner-Adams
D000981:Antiprotozoal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001331:Automation; D055808:Drug Discovery; D004351:Drug Resistance; D016829:Giardia lamblia / Q000187:drug effects* / Q000254:growth & development; D007091:Image Processing, Computer-Assisted; D008018:Life Cycle Stages / Q000187:drug effects; D021261:Parasitic Sensitivity Tests
D000981:Antiprotozoal Agents
Drug discovery; Giardia; Image-based assay; Malaria Box