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

Migla Miskinyte; John C. Dawson; Ashraff Makda; Dahlia Doughty-shenton; Neil O. Carragher; Achim Schnaufer

doi:10.1128/AAC.01980-21

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

Migla Miskinyte, John C. Dawson, Ashraff Makda, Dahlia Doughty-shenton, Neil O. Carragher, Achim Schnaufer

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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

Original language	English
Journal	Antimicrobial Agents and Chemotherapy
Early online date	6 Dec 2021
DOIs	https://doi.org/10.1128/AAC.01980-21
Publication status	E-pub ahead of print - 6 Dec 2021

Keywords / Materials (for Non-textual outputs)

High-throughput screening
high-content screening
trypanosomatids
kinetoplast
kDNA
mitochondia

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10.1128/AAC.01980-21Licence: CC BY

A novel high-content phenotypic screen to identify inhibitors of mitochondrial DNA maintenance in trypanosomesAccepted author manuscript, 5.3 MB

https://journals.asm.org/doi/10.1128/AAC.01980-21

Edinburgh Drug Discovery
Asier Unciti-Broceta (Manager), Scott Webster (Manager) & Neil Carragher (Manager)
Deanery of Molecular, Genetic and Population Health Sciences
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title = "A novel high-content phenotypic screen to identify inhibitors of mitochondrial DNA maintenance in trypanosomes",

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",

keywords = "High-throughput screening, high-content screening, trypanosomatids, kinetoplast, kDNA, mitochondia",

author = "Migla Miskinyte and Dawson, {John C.} and Ashraff Makda and Dahlia Doughty-shenton and Carragher, {Neil O.} and Achim Schnaufer",

year = "2021",

month = dec,

day = "6",

doi = "10.1128/AAC.01980-21",

language = "English",

journal = "Antimicrobial Agents and Chemotherapy",

issn = "0066-4804",

publisher = "American Society for Microbiology",

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T1 - A novel high-content phenotypic screen to identify inhibitors of mitochondrial DNA maintenance in trypanosomes

AU - Miskinyte, Migla

AU - Dawson, John C.

AU - Makda, Ashraff

AU - Doughty-shenton, Dahlia

AU - Carragher, Neil O.

AU - Schnaufer, Achim

PY - 2021/12/6

Y1 - 2021/12/6

N2 - 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

AB - 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

KW - High-throughput screening

KW - high-content screening

KW - trypanosomatids

KW - kinetoplast

KW - kDNA

KW - mitochondia

U2 - 10.1128/AAC.01980-21

DO - 10.1128/AAC.01980-21

M3 - Article

SN - 0066-4804

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

ER -

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

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

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Edinburgh Drug Discovery

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