Acquired resistance to berenil in a cloned isolate ofTrypanosoma evansiis associated with upregulation of a novel gene, TeDR40

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 inTrypanosoma 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-sensitiveT. evansifor inducible over-expression of the TeDR40 gene. Induction of over-expression of TeDR40 inT. evansiled 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 anin vitro-cultured clonal line ofT. evansi.