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

被引：13

作者：

Bhandari, Vasundhra ^{[1
]}

Kumar, Dhiraj ^{[1
]}

Verma, Sandeep ^{[1
]}

Srividya, Gurumurthy ^{[1
]}

Negi, Narendra Singh ^{[2
]}

Singh, Ruchi ^{[1
]}

Salotra, Poonam ^{[1
]}

机构：

[1] Indian Council Med Res, Natl Inst Pathol, New Delhi, India

[2] Safdarjang Hosp, Dept Med, New Delhi, India

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2013年 / 440卷 / 04期

关键词：

Visceral leishmaniasis; Drug resistance; PSA-2; Leishmania donovani; Biomarker; Antimony; AZAR DERMAL LEISHMANIASIS; LEUCINE-RICH REPEATS; VISCERAL LEISHMANIASIS; DRUG-RESISTANCE; PROTEIN; MILTEFOSINE; SUSCEPTIBILITY; IDENTIFICATION; MICROARRAYS; COMPLEMENT;

D O I：

10.1016/j.bbrc.2013.09.113

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2013 Elsevier Inc. All rights reserved.

引用

页码：646 / 651

页数：6

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