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.