Comparison of gene expression patterns among Leishmania braziliensis clinical isolates showing a different in vitro susceptibility to pentavalent antimony

V Adaui, K Schnorbusch, M Zimic, A Gutiérrez, S Decuypere, M Vanaerschot, S De Doncker, I Maes, A Llanos-Cuentas, F Chappuis, J Arévalo, JC Dujardin

    Research output: Contribution to journalA1: Web of Science-article

    Abstract

    Introduction. Evaluation of Leishmania drug susceptibility depends on in vitro SbV susceptibility assays, which are labour-intensive and may give a biased view of the true parasite resistance. Molecular markers are urgently needed to improve and simplify the monitoring of SbV-resistance. We analysed here the gene expression profile of 21 L. braziliensis clinical isolates in vitro defined as SbV-resistant and -sensitive, in order to identify potential resistance markers. Methods. The differential expression of 13 genes involved in SbV metabolism, oxidative stress or housekeeping functions was analysed during in vitro promastigote growth. Results. Expression profiles were up-regulated for 5 genes only, each time affecting a different set of isolates (mosaic picture of gene expression). Two genes, ODC (ornithine decarboxylase) and TRYR (trypanothione reductase), showed a significantly higher expression rate in the group of SbV-resistant compared to the group of SbV-sensitive parasites (P<0.01). However, analysis of individual isolates showed both markers to explain only partially the drug resistance. Discussion. Our results might be explained by (i) the occurrence of a pleiotropic molecular mechanism leading to the in vitro SbV resistance and/or (ii) the existence of different epi-phenotypes not revealed by the in vitro SbV susceptibility assays, but interfering with the gene expression patterns.
    Original languageEnglish
    JournalParasitology
    Volume138
    Issue number2
    Pages (from-to)183-193
    Number of pages11
    ISSN0031-1820
    DOIs
    Publication statusPublished - 2011

    Keywords

    • B780-tropical-medicine
    • Protozoal diseases
    • Leishmania braziliensis
    • Drug susceptibility
    • Evaluation
    • Gene expression
    • Isolation
    • In vitro
    • Assays
    • Molecular markers
    • Promastigotes
    • Antimony
    • Laboratory techniques and procedures

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