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Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites

Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, 2610 Wilrijk, Belgium
Laboratory of Medical Biochemistry (LMB), University of Antwerp, 2610 Wilrijk, Belgium
Centre de Recherche en Infectiologie du Centre de Recherche du Centre Hospitalier Universitaire de Québec, Université Laval, Québec, QC G1V 0A6, Canada
Author to whom correspondence should be addressed.
Running title—Studies into mechanisms of action and resistance in kinetoplastids.
Microorganisms 2020, 8(6), 950;
Received: 31 May 2020 / Accepted: 22 June 2020 / Published: 24 June 2020
(This article belongs to the Special Issue Treatment of Leishmaniasis)
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. View Full-Text
Keywords: kinetoplastid; resistance; target; drug; omics; mechanism; resistance kinetoplastid; resistance; target; drug; omics; mechanism; resistance
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Van den Kerkhof, M.; Sterckx, Y.G.-J.; Leprohon, P.; Maes, L.; Caljon, G. Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites. Microorganisms 2020, 8, 950.

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