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

Introduction. Evaluation of Leishmania drug susceptibility depends on in vitro Sb^V 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 Sb^V- resistance. We analysed here the gene expression profile of 21 L. braziliensis clinical isolates in vitro defined as Sb^V-resistant and -sensitive, in order to identify potential resistance markers. Methods. The differential expression of 13 genes involved in Sb^V 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 Sb^V-resistant compared to the group of Sb^V-sensitive parasites (P<001). 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 Sb ^V resistance and/or (ii) the existence of different epi-phenotypes not revealed by the in vitro Sb^V susceptibility assays, but interfering with the gene expression patterns.