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Proteomes 2015, 3(4), 328-346; doi:10.3390/proteomes3040328

Mitochondrial Proteomics of Antimony and Miltefosine Resistant Leishmania infantum

Centre de Recherche en Infectiologie du CHU de Québec, Université Laval, Québec City, QC G1V 4G2, Canada
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Academic Editor: Jacek R. Wisniewski
Received: 18 August 2015 / Revised: 7 October 2015 / Accepted: 12 October 2015 / Published: 21 October 2015
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Abstract

Antimony (SbIII) and miltefosine (MIL) are important drugs for the treatment of Leishmania parasite infections. The mitochondrion is likely to play a central role in SbIII and MIL induced cell death in this parasite. Enriched mitochondrial samples from Leishmania promastigotes selected step by step for in vitro resistance to SbIII and MIL were subjected to differential proteomic analysis. A shared decrease in both mutants in the levels of pyruvate dehydrogenase, dihydrolipoamide dehydrogenase, and isocitrate dehydrogenase was observed, as well as a differential abundance in two calcium-binding proteins and the unique dynamin-1-like protein of the parasite. Both mutants presented a shared increase in the succinyl-CoA:3-ketoacid-coenzyme A transferase and the abundance of numerous hypothetical proteins was also altered in both mutants. In general, the proteomic changes observed in the MIL mutant were less pronounced than in the SbIII mutant, probably due to the early appearance of a mutation in the miltefosine transporter abrogating the need for a strong mitochondrial adaptation. This study is the first analysis of the Leishmania mitochondrial proteome and offers powerful insights into the adaptations to this organelle during SbIII and MIL drug resistance. View Full-Text
Keywords: Leishmania; mitochondrion; proteome; antimony; miltefosine Leishmania; mitochondrion; proteome; antimony; miltefosine
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Vincent, I.M.; Racine, G.; Légaré, D.; Ouellette, M. Mitochondrial Proteomics of Antimony and Miltefosine Resistant Leishmania infantum. Proteomes 2015, 3, 328-346.

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