Characterization of natural antimony resistance in Leishmania Donovani isolates

Mittal, Mukul K. ; Rai, Smita ; Ashutosh, ; Ravinder, ; Gupta, Suman ; Sundar, Shyam ; Goyal, Neena (2007) Characterization of natural antimony resistance in Leishmania Donovani isolates American Medicine of Tropical Medicine and Hygiene, 76 (4). pp. 681-688. ISSN 0002-9637

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Official URL: http://www.ajtmh.org/content/76/4/681.short

Abstract

Clinical resistance to pentavalent antimonial compounds has long been recognized as a major problem in the treatment of visceral leishmaniasis in India. However, mechanisms of natural resistance are unclear. In this study, we observed that Leishmania donovani clinical isolates not responsive to sodium stibogluconate showed resistance to antimony treatment in both in vitro and in vivo laboratory conditions. The resistant isolates have increased levels of intracellular thiols. This increase in thiol levels was not mediated by the amplification of ?-glutamylcysteine synthetase, but was accompanied by amplification of trypanothione reductase and an intracellular ATP-binding cassette transporter gene MRPA. The resistance of parasites to antimony could be reversed by the glutathione biosynthesis-specific inhibitor, buthionine sulfoximine, which resulted in increased drug susceptibility. These results suggest the possible role of thiols and MRPA in antimony resistance in field isolates.

Item Type:Article
Source:Copyright of this article belongs to American Society of Tropical Medicine and Hygiene.
ID Code:71781
Deposited On:28 Nov 2011 04:37
Last Modified:28 Nov 2011 04:37

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