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Acquired resistance to berenil in a cloned isolate of Trypanosoma evansi is associated with upregulation of a novel gene, TeDR40

Published online by Cambridge University Press:  25 August 2005

W. H. WITOLA ,
A. TSUDA ,
N. INOUE ,
K. OHASHI  and
M. ONUMA
W. H. WITOLA
Affiliation:
Laboratory of Infectious Diseases, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan
A. TSUDA
Affiliation:
Laboratory of Infectious Diseases, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan
N. INOUE
Affiliation:
National Research Centre for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan
K. OHASHI
Affiliation:
Laboratory of Infectious Diseases, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan
M. ONUMA
Affiliation:
Laboratory of Infectious Diseases, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan
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Abstract

Drug resistance is now a severe and increasing problem in trypanosomes, but molecular details of mechanisms of resistance are only beginning to unveil. There is urgent need to clearly elucidate the different mechanisms of drug resistance in trypanosomes in order to circumvent existing resistance problems and avoid emergence of resistance to the next generation drugs. In this study, we cloned and characterized a novel gene, TeDR40, whose expression is associated with resistance to berenil in Trypanosoma evansi. Expression analysis showed that the gene was at least 1000-fold upregulated in resistant parasites and the encoded protein appeared to have a ubiquitous cellular localization. To investigate the association of TeDR40 with berenil-resistance, we genetically modified wild-type berenil-sensitive T. evansi for inducible over-expression of the TeDR40 gene. Induction of over-expression of TeDR40 in T. evansi led to decreased (P<0·01) sensitivity to berenil. Our findings indicate a possible correlation between over-expression of a novel gene, TeDR40, and reduced sensitivity to berenil in an in vitro-cultured clonal line of T. evansi.

Keywords

Trypanosoma evansiberenil resistancegene upregulationinducible gene over-expression
Type
Research Article
Information
Parasitology , Volume 131 , Issue 5 , November 2005 , pp. 635 - 646
Copyright
© 2005 Cambridge University Press

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