title: Mitochondrial Proteomics of Antimony and Miltefosine ResistantLeishmania infantum.
abstract: Antimony (SbIII) and miltefosine (MIL) are important drugs for the treatment ofLeishmaniaparasite infections. The mitochondrion is likely to play a central role in SbIII and MIL induced cell death in this parasite. Enriched mitochondrial samples fromLeishmaniapromastigotes selected step by step forin vitroresistance 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 theLeishmaniamitochondrial proteome and offers powerful insights into the adaptations to this organelle during SbIII and MIL drug resistance.
authors.affiliation: Centre de Recherche en Infectiologie du CHU de Québec, Université Laval, Québec City, QC G1V 4G2, Canada. Isabel.vincent@glasgow.ac.uk.
authors.forename: Isabel M
authors.initials: IM
authors.lastname: Vincent
authors.affiliation: Centre de Recherche en Infectiologie du CHU de Québec, Université Laval, Québec City, QC G1V 4G2, Canada. Gina.Racine@crchudequebec.ulaval.ca.
authors.forename: Gina
authors.initials: G
authors.lastname: Racine
authors.affiliation: Centre de Recherche en Infectiologie du CHU de Québec, Université Laval, Québec City, QC G1V 4G2, Canada. daniellelegare1@gmail.com.
authors.forename: Danielle
authors.initials: D
authors.lastname: Légaré
authors.affiliation: Centre de Recherche en Infectiologie du CHU de Québec, Université Laval, Québec City, QC G1V 4G2, Canada. Marc.Ouellette@crchul.ulaval.ca.
authors.forename: Marc
authors.initials: M
authors.lastname: Ouellette
keywords: Leishmania; antimony; miltefosine; mitochondrion; proteome