ArticlePLoS neglected tropical diseases2015
Over-Expression of Cysteine Leucine Rich Protein Is Related to SAG Resistance in Clinical Isolates of Leishmania donovani.
Article in PLoS neglected tropical diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Unravelling drug resistance in leishmaniasis: genomic adaptations and emerging therapies.Frontiers in molecular biosciences · 2025Review
- Antimony resistance and gene expression inParasitology · 2024Review
- Global distribution of treatment resistance gene markers for leishmaniasis.Journal of clinical laboratory analysis · 2022Review
- Transcriptome Analysis of Intracellular Amastigotes of ClinicalMicroorganisms · 2022Article
- Molecular characterization of glyceraldehyde-3-phosphate dehydrogenase from Eimeria tenella.Parasitology research · 2022Article
- Treatment failure to sodium stibogluconate in cutaneous leishmaniasis: A challenge to infection control and disease elimination.PloS one · 2021Article
- High-throughput Cos-Seq screen with intracellular Leishmania infantum for the discovery of novel drug-resistance mechanisms.International journal for parasitology. Drugs and drug resistance · 2018Article
- Understanding Leishmania parasites through proteomics and implications for the clinic.Expert review of proteomics · 2018Review
- Functional Involvement of Leishmania donovani Tryparedoxin Peroxidases during Infection and Drug Treatment.Antimicrobial agents and chemotherapy · 2018Article
- Reverse Epidemiology: An Experimental Framework to DriveFrontiers in cellular and infection microbiology · 2018Review
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Authors and funding
8 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundResistance emergence against antileishmanial drugs, particularly Sodium Antimony Gluconate (SAG) has severely hampered the therapeutic strategy against visceral leishmaniasis, the mechanism of resistance being indistinguishable. Cysteine leucine rich protein (CLrP), was recognized as one of the overexpressed proteins in resistant isolates, as observed in differential proteomics between sensitive and resistant isolates of L. donovani. The present study deals with the characterization of CLrP and for its possible connection with SAG resistance. METHODOLOGY AND PRINCIPAL
findingsIn pursuance of deciphering the role of CLrP in SAG resistance, gene was cloned, over-expressed in E. coli system and thereafter antibody was raised. The expression profile of CLrP and was found to be over-expressed in SAG resistant clinical isolates of L. donovani as compared to SAG sensitive ones when investigated by real-time PCR and western blotting. CLrP has been characterized through bioinformatics, immunoblotting and immunolocalization analysis, which reveals its post-translational modification along with its dual existence in the nucleus as well as in the membrane of the parasite. Further investigation using a ChIP assay confirmed its DNA binding potential. Over-expression of CLrP in sensitive isolate of L. donovani significantly decreased its responsiveness to SAG (SbV and SbIII) and a shift towards the resistant mode was observed. Further, a significant increase in its infectivity in murine macrophages has been observed. CONCLUSION/SIGNIFICANCE: The study reports the differential expression of CLrP in SAG sensitive and resistant isolates of L. donovani. Functional intricacy of CLrP increases with dual localization, glycosylation and DNA binding potential of the protein. Further over-expressing CLrP in sensitive isolate of L. donovani shows significantly decreased sensitivity towards SAG and increased infectivity as well, thus assisting the parasite in securing a safe niche. Results indicates the possible contribution of CLrP to antimonial resistance in L. donovani by assisting the parasite growth in the macrophages.
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