Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 66, Issue 2, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.01980-21
Keywords
high-throughput screening; high-content screening; trypanosomatids; kinetoplast; kDNA; mitochondria; Trypanosome brucei; mtDNA
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Funding
- UK Medical Research Council [MR/L019701/1]
- Institutional Strategic Support Fund (ISSF3) award [IS3-R2.28]
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In this study, we developed a high-content screen for pharmacologically induced kDNA loss in kinetoplastid parasites and identified a novel kDNA-targeting compound as a validated hit.
Kinetoplastid parasites cause diverse neglected diseases in humans and livestock, with an urgent need for new treatments. The survival of kinetoplastids depends on their uniquely structured mitochondria! genome (kDNA), the eponymous kinetoplast. Here, we report the development of a high-content screen for pharmacologically induced kDNA loss, based on specific staining of parasites and automated image analysis. As proof of concept, we screened a diverse set of similar to 14,000 small molecules and exemplify a validated hit as a novel kDNA-targeting compound.
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