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. 2021 Apr 30;10(5):1063. doi: 10.3390/cells10051063

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© 2021 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 (https://creativecommons.org/licenses/by/4.0/).

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Sb^III-resistant parasites showed a coordinated metabolomic remodeling to combat the stress caused by the drug. Yellow boxes highlight some of the effects typically caused by Sb^III in Leishmania parasites: glycolysis and β-oxidation inhibition, osmotic and oxidative stress. Green boxes highlight the group of metabolites contributing to the osmotic/oxidative balance and thiol metabolism activation. Blue boxes show the metabolites potentially contributing to the energy metabolism required to fuel thiol metabolism in the form of NADPH. This coordinated metabolic response is essential to develop resistance and combat the drug efficiently in Leishmania parasites. Metabolites increased in Sb^III-resistant parasites (↑). Metabolites decreased in Sb^III-resistant parasites (↓). Metabolites differentially detected at the intracellular (In) and extracellular levels (Ex).