A novel antifolate resistance gene on the amplified H circle of Leishmania.

摘要: In several Leishmania spp., resistance to methotrexate and other drugs is often associated with amplification of the chromosomal H region in form extrachromosomal circles. We report here that circle tarentolae contains an 867 bp open reading frame, ltdh, which mediates high levels antifolates, after transfection. The predicted amino acid sequence ltdh gene product has significant similarities a family short-chain dehydrogenases, enzymes are involved oxido-reduction reactions wide range organisms. To resist amplifies as part circle. propose LTDH might be alternative pathway for synthesis reduced folates overproduction represents novel mechanism antifolates. Our results support hypothesis genome drug genes preferential this evolved defense against cytotoxic drugs.