title: Differential expression of proteins in antimony-susceptible and -resistant isolates of Leishmania donovani.
abstract: Visceral Leishmaniasis (VL) is a parasitic disease caused by the protozoan parasite Leishmania donovani. Resistance to pentavalent antimonials (SbV), the mainstay therapy for leishmaniasis is now a major concern, due to emergence of drug resistance. Hence, understanding the underlying mechanism of resistance to antimonials is required. Here we used quantitative mass spectrometery to identify global proteome differences between antimony-susceptible/-resistant isolates. We detected modification of expression of proteins involved in the key metabolic pathways. Comparative proteomic analysis indicated increase in glycolysis in the antimony-resistant isolates. Elevated expression of stress related proteins implicated in oxidative stress was observed in the resistant parasites. Most importantly, we observed upregulation of proteins that may have a role in intracellular survival of the parasite in the resistant isolates. The identified parasite proteins could serve as surrogate markers for resistance or susceptibility and would also help in understanding the underlying mechanism of resistance to antimonials.
authors: School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
authors: Neha
authors: N
authors: Biyani
authors: Alok Kumar
authors: AK
authors: Singh
authors: Swati
authors: S
authors: Mandal
authors: Bhavna
authors: B
authors: Chawla
authors: Rentala
authors: R
authors: Madhubala
mesh_terms: D000965:Antimony / Q000494:pharmacology*; D015415:Biomarkers / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D015536:Down-Regulation; D004351:Drug Resistance; D006019:Glycolysis; D006360:Heat-Shock Proteins / Q000378:metabolism; D007893:Leishmania donovani / Q000187:drug effects* / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods; D018384:Oxidative Stress; D020543:Proteome / Q000032:analysis / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D006360:Heat-Shock Proteins; D020543:Proteome; D015800:Protozoan Proteins; D012269:Ribosomal Proteins; D014404:Tubulin; D000965:Antimony