Abstract
Miltefosine is the first oral drug used in chemotherapy against leishmaniasis. In vitro studies found that resistance to miltefosine in Leishmania is often associated with the acquisition of point mutations in the miltefosine transporter, leading to a decrease in drug uptake. In this study, the dynamics of mutations upon miltefosine selection was studied by deep-sequencing of the miltefosine transporter gene. Deep-sequencing data revealed that no mutation was detected in the miltefosine transporter at sub-inhibitory concentrations of miltefosine. We show that the prevalence of mutated alleles was increasing when the drug pressure heightened, that more mutations were observed in highly resistant mutants, and that most mutations remained when parasites were cultured for a few passages in the absence of miltefosine.
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MCNL is a recipient of a “Bourse de Leadership et Développement Durable du SPUL” (Syndicat des Professeurs de l’Université Laval), MO holds a Canada Research Chair in Antimicrobial Resistance. This work was supported by the Canadian Institutes of Health Research (15501 to MO).
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Laffitte, MC.N., Leprohon, P., Légaré, D. et al. Deep-sequencing revealing mutation dynamics in the miltefosine transporter gene in Leishmania infantum selected for miltefosine resistance. Parasitol Res 115, 3699–3703 (2016). https://doi.org/10.1007/s00436-016-5195-y
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DOI: https://doi.org/10.1007/s00436-016-5195-y