Acquired resistance to berenil in a cloned isolate of Trypanosoma evansi is associated with upregulation of a novel gene, TeDR40
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.(Received January 12 2005)
(Revised March 28 2005)
(Revised April 22 2005)
(Accepted May 24 2005)
Key Words: Trypanosoma evansi; berenil resistance; gene upregulation; inducible gene over-expression.
c1 Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan. Tel: +81 11 7065215. Fax: +81 11 7065217. E-mail: firstname.lastname@example.org