Segovia M
Departamento de Genética y Microbiología, Facultad de Medicina, Universidad de Murcia, Spain.
Ann Trop Med Parasitol. 1994 Apr;88(2):123-30. doi: 10.1080/00034983.1994.11812849.
Leishmania spp. are excellent models for analysing the mechanisms of drug resistance, one of the major barriers to the treatment and control of several major diseases. They may become refractory to drugs as the result of gene amplification. Amplified Leishmania DNA are extrachromosomal, usually circular, and arise from a source chromosome. Several multicopy extrachromosomal DNA have been identified, either spontaneously in unselected stocks or, more commonly, in response to multiple rounds of step-wise increases in drug concentration. R circles, G circles and ODC140-L minichromosomes are extrachromosomal amplifications encoding copies of dihydrofolate reductase-thymidylate synthase, glycosyltransferase, and ornithine decarboxylase, respectively, and conferring resistance to inhibitors of these gene products (methotrexate, tunicamycin and alpha-difluoromethylornithine, respectively). Another DNA amplification, named the H circle, has been detected in response to several unrelated drugs and confers drug resistance. Leishmania spp. represent a unique model since, even without drug pressure, gene amplifications appear and remain as extrachromosomal circular and linear amplicons. The CD1/LD1 elements, of unknown biological role, arise de novo in cultures in the absence of drug pressure.
利什曼原虫属是分析耐药机制的优秀模型，耐药是几种主要疾病治疗和控制的主要障碍之一。由于基因扩增，它们可能对药物产生耐药性。扩增的利什曼原虫DNA是染色体外的，通常是环状的，来源于一条源染色体。已经鉴定出几种多拷贝染色体外DNA，它们要么在未选择的菌株中自发出现，要么更常见的是在药物浓度逐步多次增加的情况下出现。R环、G环和ODC140-L微型染色体是染色体外扩增产物，分别编码二氢叶酸还原酶-胸苷酸合成酶、糖基转移酶和鸟氨酸脱羧酶的拷贝，并赋予对这些基因产物抑制剂（分别为甲氨蝶呤、衣霉素和α-二氟甲基鸟氨酸）的抗性。另一种名为H环的DNA扩增已在对几种不相关药物的反应中被检测到，并赋予耐药性。利什曼原虫属代表了一个独特的模型，因为即使没有药物压力，基因扩增也会出现并以染色体外环状和线性扩增子的形式存在。CD1/LD1元件的生物学作用尚不清楚，在没有药物压力的培养物中会重新出现。
