1921
Volume 76, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

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 clinical isolates not responsive to sodium stibogluconate showed resistance to antimony treatment in both and laboratory conditions. The resistant isolates have increased levels of intracellular thiols. This increase in thiol levels was not mediated by the amplification of γ-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.

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  • Received : 12 Sep 2006
  • Accepted : 22 Nov 2006

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