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Biochem Biophys Res Commun. 2013 Nov 1;440(4):646-51. doi: 10.1016/j.bbrc.2013.09.113. Epub 2013 Oct 5.

Increased parasite surface antigen-2 expression in clinical isolates of Leishmania donovani augments antimony resistance.

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  • 1National Institute of Pathology, Indian Council of Medical Research, Safdarjung Hospital Campus, New Delhi, India.

Abstract

Resistance to sodium antimony gluconate (SAG) is a major cause of therapeutic failure in a large proportion of visceral leishmaniasis (VL) cases. Determinants of SAG resistance have been widely studied; however, the mechanism operating in clinical isolates is poorly understood. In the present study, expression of parasite surface antigen-2 (PSA-2) gene was studied in clinical isolates of Leishmania donovani comprising of antimony resistant (n=10) and sensitive (n=4) parasites. The expression of PSA-2 gene was found to be consistently high in SAG resistant clinical isolates (≥1.5-fold) at both transcript and protein level. Further, over-expression of PSA-2 in L. donovani isolates (LdPSA-2(++)) resulted in conversion of SAG sensitive phenotype to resistant. The LdPSA-2(++) parasites showed significantly decreased susceptibility towards SAG (>12-fold), amphotericin B (>4-fold) and miltefosine (>2.5-fold). Marked decrease in antimony accumulation and enhanced tolerance towards complement mediated lysis was evident in LdPSA-2(++) parasites. The study established the role of PSA-2 gene in SAG resistance and its potential as a biomarker to distinguish resistant and sensitive clinical isolates of L. donovani.

Copyright © 2013 Elsevier Inc. All rights reserved.

KEYWORDS:

Antimony; Biomarker; Drug resistance; Leishmania donovani; PSA-2; Visceral leishmaniasis

PMID:
24103752
[PubMed - indexed for MEDLINE]
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