Quantitative secretome analysis unravels new secreted proteins in Amphotericin B resistant Leishmania donovani
Author(s)
Garg, G
Ali, V
Singh, K
Gupta, P
Ganguly, A
Sahasrabuddhe, AA
Das, P
Year published
2019
Metadata
Show full item recordAbstract
Leishmaniasis is second most neglected disease after malaria and seems to be a worldwide concern because of increased drug resistance and non-availability of approved vaccine. The underlying molecular mechanism of drug resistance (Amp B) in Leishmania parasites still remains elusive. Herein, the present study investigated differentially expressed secreted proteins of Amphotericin B sensitive (S) and resistant (R) isolate of Leishmania donovani by using label free quantitative LC-MS/MS approach. A total of 406 differentially expressed secreted proteins were found between sensitive (S) and resistant (R) isolate. Among 406 ...
View more >Leishmaniasis is second most neglected disease after malaria and seems to be a worldwide concern because of increased drug resistance and non-availability of approved vaccine. The underlying molecular mechanism of drug resistance (Amp B) in Leishmania parasites still remains elusive. Herein, the present study investigated differentially expressed secreted proteins of Amphotericin B sensitive (S) and resistant (R) isolate of Leishmania donovani by using label free quantitative LC-MS/MS approach. A total of 406 differentially expressed secreted proteins were found between sensitive (S) and resistant (R) isolate. Among 406 proteins, 32 were significantly up regulated (>2.0 fold) while 22 were down regulated (<0.5 fold) in resistant isolate of L. donovani. Further, differentially expressed proteins were classified into 11 various biological processes. Interestingly, identified up regulated proteins in resistant parasites were dominated in carbohydrate metabolism, stress response, transporters and proteolysis. Western blot and enzymatic activity of identified proteins validate our proteomic findings. Finally, our study demonstrated some new secreted proteins associated with Amp B resistance which provides a basis for further investigations to understand the role of proteins in L. donovani. Biological significance: Although great advances have been achieved in the diagnosis and treatment of leishmaniasis, still drug resistance is major hurdle in control of disease. Present study will enhance the deeper understanding of altered metabolic pathways involved in Amp B resistance mechanism and provide possible new proteins which can be potential candidate either for exploring as new drug target or vaccine. Protein-protein interactions highlighted the up-regulated metabolic pathways in resistant parasites which further unravel the adaptive mechanism of parasites.
View less >
View more >Leishmaniasis is second most neglected disease after malaria and seems to be a worldwide concern because of increased drug resistance and non-availability of approved vaccine. The underlying molecular mechanism of drug resistance (Amp B) in Leishmania parasites still remains elusive. Herein, the present study investigated differentially expressed secreted proteins of Amphotericin B sensitive (S) and resistant (R) isolate of Leishmania donovani by using label free quantitative LC-MS/MS approach. A total of 406 differentially expressed secreted proteins were found between sensitive (S) and resistant (R) isolate. Among 406 proteins, 32 were significantly up regulated (>2.0 fold) while 22 were down regulated (<0.5 fold) in resistant isolate of L. donovani. Further, differentially expressed proteins were classified into 11 various biological processes. Interestingly, identified up regulated proteins in resistant parasites were dominated in carbohydrate metabolism, stress response, transporters and proteolysis. Western blot and enzymatic activity of identified proteins validate our proteomic findings. Finally, our study demonstrated some new secreted proteins associated with Amp B resistance which provides a basis for further investigations to understand the role of proteins in L. donovani. Biological significance: Although great advances have been achieved in the diagnosis and treatment of leishmaniasis, still drug resistance is major hurdle in control of disease. Present study will enhance the deeper understanding of altered metabolic pathways involved in Amp B resistance mechanism and provide possible new proteins which can be potential candidate either for exploring as new drug target or vaccine. Protein-protein interactions highlighted the up-regulated metabolic pathways in resistant parasites which further unravel the adaptive mechanism of parasites.
View less >
Journal Title
Journal of Proteomics
Volume
207
Subject
Biochemistry and cell biology
Plant biology
Medical biochemistry and metabolomics
Diagnosis
Drug resistance
Drug target
Proteomics
Secreted proteins