title: Miltefosine-unresponsive Leishmania donovani has a greater ability than miltefosine-responsive L. donovani to resist reactive oxygen species.
abstract: Resistance of Leishmania 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 Leishmania 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.
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Guwahati, Assam, India.
authors.forename: Mousumi
authors.initials: M
authors.lastname: Das
authors.forename: Prakash
authors.initials: P
authors.lastname: Saudagar
authors.forename: Shyam
authors.initials: S
authors.lastname: Sundar
authors.forename: Vikash K
authors.initials: VK
authors.lastname: Dubey
mesh_terms: D002118:Calcium / Q000378:metabolism; D004351:Drug Resistance; D005434:Flow Cytometry; D007893:Leishmania donovani / Q000187:drug effects* / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins; D017382:Reactive Oxygen Species; D010767:Phosphorylcholine; C039128:miltefosine; D002118:Calcium
keywords: enzyme inhibition; leishmaniasis; miltefosine resistance; protein biochemistry