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药物抗性已成为几种主要疾病的治疗和控制的重要障碍之一,而利什曼原虫是分析这一机制的优良模型。由于基因扩增以致对药物产生抗性。扩增的利什曼原虫DNA源于染色体,通常为环状的染色体外DNA。已鉴定了数个多拷贝的染色体外DNA,有的来自自发的、未经选择的虫株,更为常见的是来自对多周期逐渐增加浓度的药物反应。R环、G环和ODC140-L微型染色体均为扩增的染色体外DNA,依次编码二氢叶酸还原酶-胸苷酸合成酶、糖基转移酶和鸟苷酸脱羧酶,并赋于对这些基因产物的抑制剂(依次为甲氨蝶呤、衣霉素和α-二氟甲基鸟苷酸)的抗性。在对几种无关联药物的反应中检出了称为H环的另一DNA扩增,并能提供药物抗性。由于利什曼原虫甚至在无药物压力下也可出现基因扩增并以染色体外环状和线状扩增子形式保留,它代表了一种独特的模型。生物学作用未知的CD1/LD1成分,是在无药物压力的培养中从头产生的。
Drug resistance has become one of the major obstacles in the treatment and control of several major diseases, and Leishmania is an excellent model for analyzing this mechanism. Drug resistance due to gene amplification. The amplified Leishmania DNA is derived from the chromosome, usually circular extrachromosomal DNA. Several multicopy extrachromosomal DNAs have been identified, some from spontaneous, unselected strains, and more commonly from drug reactions that progressively increase concentrations over multiple cycles. The R, G and ODC140-L minichromosomes are all amplified extrachromosomal DNAs, which in turn encode dihydrofolate reductase-thymidylate synthase, glycosyltransferase and guanylate decarboxylase and confer upon these Resistance to gene products (followed by methotrexate, tunicamycin and alpha-difluoromethyl guanosine). Another DNA amplification known as the H-ring was detected in response to several unrelated drugs and provided drug resistance. Leishmania represents a unique model because gene amplification can occur even under drug-free stress and remains as extrachromosomal circular and linear amplicons. The biological role of unknown CD1 / LD1 components, is produced in the absence of drug stress in the head.