title: Acquired resistance to berenil in a cloned isolate of Trypanosoma evansi is 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 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.
authors.affiliation: Laboratory of Infectious Diseases, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: W H
authors.initials: WH
authors.lastname: Witola
authors.forename: A
authors.initials: A
authors.lastname: Tsuda
authors.forename: N
authors.initials: N
authors.lastname: Inoue
authors.forename: K
authors.initials: K
authors.lastname: Ohashi
authors.forename: M
authors.initials: M
authors.lastname: Onuma
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004133:Diminazene / Q000031:analogs & derivatives* / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics*; D017125:Genes, Protozoan / Q000235:genetics*; D008969:Molecular Sequence Data; D015800:Protozoan Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014345:Trypanosoma / Q000187:drug effects* / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects* / Q000235:genetics
chemical_list: D015800:Protozoan Proteins; D012333:RNA, Messenger; D014344:Trypanocidal Agents; C003915:diminazene aceturate; D004133:Diminazene