Genomic and transcriptomic alterations in Leishmania donovani lines experimentally resistant to antileishmanial drugs

Publication date: Available online 13 April 2018 Source:International Journal for Parasitology: Drugs and Drug Resistance Author(s): Alberto Rastrojo, Raquel García-Hernández, Paola Vargas, Esther Camacho, Laura Corvo, Hideo Imamura, Jean-Claude Dujardin, Santiago Castanys, Begoña Aguado, Francisco Gamarro, Jose M. Requena Leishmaniasis is a serious medical issue in many countries around the World, but it remains largely neglected in terms of research investment for developing new control and treatment measures. No vaccines exist for human use, and the chemotherapeutic agents currently used are scanty. Furthermore, for some drugs, resistance and treatment failure are increasing to alarming levels. The aim of this work was to identify genomic and trancriptomic alterations associated with experimental resistance against the common drugs used against VL: trivalent antimony (SbIII, S line), amphotericin B (AmB, A line), miltefosine (MIL, M line) and paromomycin (PMM, P line). A total of 1006 differentially expressed transcripts were identified in the S line, 379 in the A line, 146 in the M line, and 129 in the P line. Also, changes in ploidy of chromosomes and amplification/deletion of particular regions were observed in the resistant lines regarding the parental one. A series of genes were identified as possible drivers of the resistance phenotype and were validated by transfection experiments in both promastigotes and amastigotes from Leishmania donovani, Leishm...
Source: International Journal for Parasitology: Drugs and Drug Resistance - Category: Parasitology Source Type: research