A novel high-content phenotypic screen to identify inhibitors of mitochondrial DNA maintenance in trypanosomes

Author:

Miskinyte Migla1,Dawson John C.2,Makda Ashraff2,Doughty-Shenton Dahlia3,Carragher Neil O.2,Schnaufer Achim1ORCID

Affiliation:

1. Institute of Immunology & Infection Research, University of Edinburgh, Edinburgh, United Kingdom

2. Cancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, United Kingdom

3. MRC Centre for Reproductive Health, The Queen's Medical Research Institute, University of Edinburgh, United Kingdom

Abstract

Kinetoplastid parasites cause diverse neglected diseases in humans and livestock, with an urgent need for new treatments. Survival of kinetoplastids depends on their uniquely structured mitochondrial genome (kDNA), the eponymous kinetoplast. Here we report 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 ∼14,000 small molecules and exemplify a validated hit as a novel kDNA-targeting compound.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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