Leishmania gene amplification: a mechanism of drug resistance.

摘要: Leishmania spp. are excellent models for analysing the mechanisms of drug resistance, one major barriers to treatment and control several diseases. They may become refractory drugs as result gene amplification. Amplified DNA extrachromosomal, usually circular, arise from a source chromosome. Several multicopy extrachromosomal have been identified, either spontaneously in unselected stocks or, more commonly, response multiple rounds step-wise increases concentration. R circles, G circles ODC140-L minichromosomes amplifications encoding copies dihydrofolate reductase-thymidylate synthase, glycosyltransferase, ornithine decarboxylase, respectively, conferring resistance inhibitors these products (methotrexate, tunicamycin alpha-difluoromethylornithine, respectively). Another amplification, named H circle, has detected unrelated confers resistance. represent unique model since, even without pressure, appear remain circular linear amplicons. The CD1/LD1 elements, unknown biological role, de novo cultures absence pressure.