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

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• 作者：Vasundhra Bh ; ari ; Dhiraj Kumar ; S ; eep Verma ; Gurumurthy Srividya ; Narendra Singh Negi ; Ruchi Singh ; Poonam Salotra
• 关键词：Visceral leishmaniasis ; Drug resistance ; PSA-2 ; Leishmania donovani ; Biomarker ; Antimony
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：1 November, 2013
• 年：2013
• 卷：440
• 期：4
• 页码：646-651
• 全文大小：953 K

文摘

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 (猢?.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.