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  • 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
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    Abstract
    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 ...
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    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.
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    Journal Title
    Journal of Proteomics
    Volume
    207
    DOI
    https://doi.org/10.1016/j.jprot.2019.103464
    Subject
    Biochemistry and cell biology
    Plant biology
    Medical biochemistry and metabolomics
    Diagnosis
    Drug resistance
    Drug target
    Proteomics
    Secreted proteins
    Publication URI
    http://hdl.handle.net/10072/406773
    Collection
    • Journal articles

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