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Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites †

Kinetoplastids are the causative agents of leishmaniasis, human African trypanosomiasis, and American trypanosomiasis. They are responsible for high mortality and morbidity in (sub)tropical regions. Adequate treatment options are limited and have several drawbacks, such as toxicity, need for parente...

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Autores principales: Van den Kerkhof, Magali, Sterckx, Yann G.-J., Leprohon, Philippe, Maes, Louis, Caljon, Guy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356981/
https://www.ncbi.nlm.nih.gov/pubmed/32599761
http://dx.doi.org/10.3390/microorganisms8060950
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author Van den Kerkhof, Magali
Sterckx, Yann G.-J.
Leprohon, Philippe
Maes, Louis
Caljon, Guy
author_facet Van den Kerkhof, Magali
Sterckx, Yann G.-J.
Leprohon, Philippe
Maes, Louis
Caljon, Guy
author_sort Van den Kerkhof, Magali
collection PubMed
description Kinetoplastids are the causative agents of leishmaniasis, human African trypanosomiasis, and American trypanosomiasis. They are responsible for high mortality and morbidity in (sub)tropical regions. Adequate treatment options are limited and have several drawbacks, such as toxicity, need for parenteral administration, and occurrence of treatment failure and drug resistance. Therefore, there is an urgency for the development of new drugs. Phenotypic screening already allowed the identification of promising new chemical entities with anti-kinetoplastid activity potential, but knowledge on their mode-of-action (MoA) is lacking due to the generally applied whole-cell based approach. However, identification of the drug target is essential to steer further drug discovery and development. Multiple complementary techniques have indeed been used for MoA elucidation. In this review, the different ‘omics’ approaches employed to define the MoA or mode-of-resistance of current reference drugs and some new anti-kinetoplastid compounds are discussed.
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spelling pubmed-73569812020-07-23 Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites † Van den Kerkhof, Magali Sterckx, Yann G.-J. Leprohon, Philippe Maes, Louis Caljon, Guy Microorganisms Review Kinetoplastids are the causative agents of leishmaniasis, human African trypanosomiasis, and American trypanosomiasis. They are responsible for high mortality and morbidity in (sub)tropical regions. Adequate treatment options are limited and have several drawbacks, such as toxicity, need for parenteral administration, and occurrence of treatment failure and drug resistance. Therefore, there is an urgency for the development of new drugs. Phenotypic screening already allowed the identification of promising new chemical entities with anti-kinetoplastid activity potential, but knowledge on their mode-of-action (MoA) is lacking due to the generally applied whole-cell based approach. However, identification of the drug target is essential to steer further drug discovery and development. Multiple complementary techniques have indeed been used for MoA elucidation. In this review, the different ‘omics’ approaches employed to define the MoA or mode-of-resistance of current reference drugs and some new anti-kinetoplastid compounds are discussed. MDPI 2020-06-24 /pmc/articles/PMC7356981/ /pubmed/32599761 http://dx.doi.org/10.3390/microorganisms8060950 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Van den Kerkhof, Magali
Sterckx, Yann G.-J.
Leprohon, Philippe
Maes, Louis
Caljon, Guy
Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites †
title Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites †
title_full Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites †
title_fullStr Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites †
title_full_unstemmed Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites †
title_short Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites †
title_sort experimental strategies to explore drug action and resistance in kinetoplastid parasites †
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356981/
https://www.ncbi.nlm.nih.gov/pubmed/32599761
http://dx.doi.org/10.3390/microorganisms8060950
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