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

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.

• Authors: Vasundhra Bhandari, Dhiraj Kumar, Sandeep Verma, Gurumurthy Srividya, Narendra Singh Negi, Ruchi Singh, Poonam Salotra
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 440 Issue 4 Pg. 646-51 (Nov 01 2013) ISSN: 1090-2104 [Electronic] United States
• PMID: 24103752 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Antigens, Protozoan
• Antigens, Surface
• Protozoan Proteins
• Trypanocidal Agents
• surface antigen P2, Leishmania
• Amphotericin B
• Antimony Sodium Gluconate

Topics

• Amphotericin B (pharmacology)
• Antigens, Protozoan (genetics)
• Antigens, Surface (genetics)
• Antimony Sodium Gluconate (pharmacology, therapeutic use)
• Drug Resistance (genetics)
• Humans
• Leishmania donovani (drug effects, genetics, isolation & purification)
• Leishmaniasis, Visceral (drug therapy, parasitology)
• Protozoan Proteins (genetics)
• Trypanocidal Agents (pharmacology)