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Proteomic analysis of wild type and arsenite-resistant Leishmania donovani
Shruti Sharma1, Gaganmeet Singh, Hemantkumar D Chavan
1Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER)(2), Sector 67, S.A.S. Nagar, Punjab 160 062, India.
Abstract:
Leishmania donovani, causative organism for visceral leishmaniasis, is responsible for considerable mortality and morbidity worldwide. Generation of drug-resistant variants continue to challenge the chemotherapy, the mainstay to fight the disease. The aim of current study was proteomic profiling of wild type (Ld-Wt) and arsenite-resistant (Ld-As20) L. donovani. Significant differences in protein profiles were observed between Ld-As20 and its parent Ld-Wt strain. Proteomic analysis of 158 spots from Ld-Wt and 144 spots from, Ld-As20 identified 77 and 74 protein entries, respectively, through MALDI-TOF/TOF based mass spectrometry and database search. A shift in the isoelectric point of few proteins was observed both in Ld-Wt and Ld-As20, which raises the possibility of continuous arsenite stress, resulting in the differences in the protein profiles of drug-resistant strain from its parent wild type strain. The comparative proteomic data holds the key for elucidation of the multifactorial and complex drug resistance mechanism, like arsenite resistance, in the parasite.
Insights
This study compared protein profiles of wild type and arsenite-resistant Leishmania donovani. Proteomic analysis revealed significant differences, offering insights into drug resistance mechanisms in visceral leishmaniasis parasites.
Area of Science:
- Parasitology
- Proteomics
- Molecular Biology
Background:
- Visceral leishmaniasis, caused by Leishmania donovani, presents a global health challenge due to significant mortality and morbidity.
- The emergence of drug-resistant Leishmania donovani strains complicates chemotherapy, necessitating research into resistance mechanisms.
Purpose of the Study:
- To perform a comparative proteomic profiling of wild-type (Ld-Wt) and arsenite-resistant (Ld-As20) Leishmania donovani strains.
- To identify differences in protein expression that may explain arsenite resistance in Leishmania donovani.
Main Methods:
- Comparative proteomic analysis using MALDI-TOF/TOF based mass spectrometry.
- Identification of protein entries by database searching.
- Analysis of protein spot differences and shifts in isoelectric points between resistant and wild-type strains.
Main Results:
- Significant differences in protein profiles were observed between Ld-As20 and Ld-Wt strains.
- Proteomic analysis identified 77 protein entries in Ld-Wt and 74 in Ld-As20.
- Observed shifts in isoelectric points suggest continuous arsenite stress influencing protein profiles.
Conclusions:
- Comparative proteomic data provides a foundation for understanding the complex mechanisms of arsenite resistance in Leishmania donovani.
- The identified protein differences are crucial for elucidating multifactorial drug resistance in this parasite.
- Further research into these proteomic alterations can guide the development of novel therapeutic strategies against visceral leishmaniasis.
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