Miltefosine‐unresponsive L eishmania donovani has a greater ability than miltefosine‐responsive L . donovani to resist reactive oxygen species

Resistance of L eishmania parasites to miltefosine, which is only available oral drug, is a great concern. We have analyzed global gene expression profiles of miltefosine‐unresponsive and miltefosine‐responsive L eishmania donovani in order to understand the various metabolic processes involved in miltefosine drug resistance. The microarray data clearly indicated a role of oxidative metabolism in miltefosine resistance. Furthermore, fluorescence microscopy experiments suggested that miltefosine‐unresponsive L . donovani resists the accumulation of reactive oxygen species and subsequent mitochondrial membrane damage leading to apoptotic death. In contrast, in miltefosine‐responsive L . donovani , the accumulation of reactive oxygen species causes apoptotic death. Overall, this study provides fundamental insights into miltefosine resistance in L . donovani . Database The microarray data have been deposited in the G ene E xpression O mnibus database under the accession number GSE 45496