High-throughput Giardia lamblia viability assay using bioluminescent ATP content measurements.

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TitleHigh-throughput Giardia lamblia viability assay using bioluminescent ATP content measurements.
Publication TypeJournal Article
Year of Publication2011
AuthorsChen, CZ, Kulakova, L, Southall, N, Marugan, JJ, Galkin, A, Austin, CP, Herzberg, O, Zheng, W
JournalAntimicrob Agents Chemother
Volume55
Issue2
Pagination667-75
Date Published2011 Feb
ISSN1098-6596
KeywordsAdenosine Triphosphate, Animals, Antiprotozoal Agents, CHO Cells, Cricetinae, Cricetulus, Cyclohexanes, Drug Discovery, Fatty Acids, Unsaturated, Giardia lamblia, High-Throughput Screening Assays, Humans, Luminescent Measurements, Parasitic Sensitivity Tests, Sesquiterpenes, Trophozoites
Abstract

The human pathogen Giardia lamblia is an anaerobic protozoan parasite that causes giardiasis, one of the most common diarrheal diseases worldwide. Although several drugs are available for the treatment of giardiasis, drug resistance has been reported and is likely to increase, and recurrent infections are common. The search for new drugs that can overcome the drug-resistant strains of Giardia is an unmet medical need. New drug screen methods can facilitate the drug discovery process and aid with the identification of new drug targets. Using a bioluminescent ATP content assay, we have developed a phenotypic drug screen method to identify compounds that act against the actively growing trophozoite stage of the parasite. This assay is homogeneous, robust, and suitable for high-throughput screening of large compound collections. A screen of 4,096 pharmacologically active small molecules and approved drugs revealed 43 compounds with selective anti-Giardia properties, including 32 previously reported and 11 novel anti-Giardia agents. The most potent novel compound was fumagillin, which showed 50% inhibitory concentrations of 10 nM against the WB isolate and 2 nM against the GS isolate.

DOI10.1128/AAC.00618-10
Alternate JournalAntimicrob. Agents Chemother.
PubMed ID21078930
PubMed Central IDPMC3028786
Grant ListR01 AI059733 / AI / NIAID NIH HHS / United States