A Novel High-Content Phenotypic Screen To Identify Inhibitors of Mitochondrial DNA Maintenance in Trypanosomes

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 mitochondrial genome (kDNA), the eponymous kinetoplast. Here, we report the development of a high-content scre...

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Autores principales: Miskinyte, Migla, Dawson, John C., Makda, Ashraff, Doughty-Shenton, Dahlia, Carragher, Neil O., Schnaufer, Achim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Mechanisms of Action: Physiological Effects
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8846439/
https://www.ncbi.nlm.nih.gov/pubmed/34871097
http://dx.doi.org/10.1128/AAC.01980-21
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author Miskinyte, Migla
Dawson, John C.
Makda, Ashraff
Doughty-Shenton, Dahlia
Carragher, Neil O.
Schnaufer, Achim
author_facet Miskinyte, Migla
Dawson, John C.
Makda, Ashraff
Doughty-Shenton, Dahlia
Carragher, Neil O.
Schnaufer, Achim
author_sort Miskinyte, Migla
collection PubMed
description 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 mitochondrial 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 ∼14,000 small molecules and exemplify a validated hit as a novel kDNA-targeting compound.
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spelling pubmed-88464392022-03-03 A Novel High-Content Phenotypic Screen To Identify Inhibitors of Mitochondrial DNA Maintenance in Trypanosomes Miskinyte, Migla Dawson, John C. Makda, Ashraff Doughty-Shenton, Dahlia Carragher, Neil O. Schnaufer, Achim Antimicrob Agents Chemother Mechanisms of Action: Physiological Effects 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 mitochondrial 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 ∼14,000 small molecules and exemplify a validated hit as a novel kDNA-targeting compound. American Society for Microbiology 2022-02-15 /pmc/articles/PMC8846439/ /pubmed/34871097 http://dx.doi.org/10.1128/AAC.01980-21 Text en Copyright © 2022 Miskinyte et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Mechanisms of Action: Physiological Effects
Miskinyte, Migla
Dawson, John C.
Makda, Ashraff
Doughty-Shenton, Dahlia
Carragher, Neil O.
Schnaufer, Achim
A Novel High-Content Phenotypic Screen To Identify Inhibitors of Mitochondrial DNA Maintenance in Trypanosomes
title A Novel High-Content Phenotypic Screen To Identify Inhibitors of Mitochondrial DNA Maintenance in Trypanosomes
title_full A Novel High-Content Phenotypic Screen To Identify Inhibitors of Mitochondrial DNA Maintenance in Trypanosomes
title_fullStr A Novel High-Content Phenotypic Screen To Identify Inhibitors of Mitochondrial DNA Maintenance in Trypanosomes
title_full_unstemmed A Novel High-Content Phenotypic Screen To Identify Inhibitors of Mitochondrial DNA Maintenance in Trypanosomes
title_short A Novel High-Content Phenotypic Screen To Identify Inhibitors of Mitochondrial DNA Maintenance in Trypanosomes
title_sort novel high-content phenotypic screen to identify inhibitors of mitochondrial dna maintenance in trypanosomes
topic Mechanisms of Action: Physiological Effects
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8846439/
https://www.ncbi.nlm.nih.gov/pubmed/34871097
http://dx.doi.org/10.1128/AAC.01980-21
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