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首页> 外文期刊>Journal of Molecular Biology >BETA-TUBULIN GENES FROM THE PARASITIC NEMATODE HAEMONCHUS CONTORTUS MODULATE DRUG RESISTANCE IN CAENORHABDITIS ELEGANS
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BETA-TUBULIN GENES FROM THE PARASITIC NEMATODE HAEMONCHUS CONTORTUS MODULATE DRUG RESISTANCE IN CAENORHABDITIS ELEGANS

机译：寄生线虫嗜血杆菌的β-微管蛋白基因可调节拟南芥中的抗药性

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Resistance to antimitotic chemotherapeutics in pathogenic nematodes, fungi and mammalian cells is closely associated with structural changes in cytoskeletal beta-tubulin. We investigated the possibility of using the well-characterised free-living nematode Caenorhabditis elegans as a model for studying the mechanism of resistance against benzimidazole (BZ) drugs in the parasitic nematode Haemonchus contortus. Functional analysis of a conserved beta-tubulin isotype (tub-1) mutation near GTP-binding domain II, which is linked to BZ resistance, was carried out in C. elegans by heterologous expression of: (1) parasite BZ-sensitive alleles; (2) BZ-resistant alleles; and (3) in vitro mutagenised beta-tubulin gene constructs. The injected heterologous gene constructs were not only stably maintained, but also expressed as shown by reverse transcriptase-polymerase chain reaction analysis. The degree of BZ drug susceptibility of the transformants was assayed and quantified by incubation with both benomyl and thiabendazol. All H. contortus tub-1 constructs, which encoded Phe at position 200, conferred susceptibility to thiabendazole in BZ-resistant C. elegans ben-1 mutants. In contrast, constructs carrying Tyr200 did not alter the BZ drug phenotype. From these experiments we conclude that: (1) C. elegans can be used as an expression host, since injected parasite genes were biologically active; and (2) the single Phe to Tyr mutation at position 200 in beta-tubulin isotype 1 is the cause of BZ resistance in H. contortus. [References: 36]
机译：病原线虫，真菌和哺乳动物细胞对抗有丝分裂化学疗法的抗性与细胞骨架β微管蛋白的结构变化密切相关。我们调查了使用特征明确的自由生活线虫秀丽隐杆线虫作为研究寄生性线虫Haemonchus contortus对苯并咪唑（BZ）药物耐药机制的模型的可能性。通过异源表达在秀丽隐杆线虫中对与BZ抗性相关的GTP结合域II附近的保守β-微管蛋白同型（tub-1）突变进行功能分析：（1）寄生虫对BZ敏感的等位基因; （2）抗BZ等位基因; （3）体外诱变的β-微管蛋白基因构建体。注射的异源基因构建体不仅被稳定地维持，而且还通过逆转录酶-聚合酶链反应分析显示出来。通过与苯菌灵和噻菌灵一起孵育来测定和定量转化体的BZ药物敏感性程度。所有在200位编码Phe的Contortus tub-1构造均赋予抗BZ秀丽隐杆线虫ben-1突变体对噻菌灵的敏感性。相反，携带Tyr200的构建体不会改变BZ药物表型。从这些实验中我们得出以下结论：（1）秀丽隐杆线虫可以用作表达宿主，因为注射的寄生虫基因具有生物活性; （2）β-微管蛋白同种型1中第200位的单Phe到Tyr突变是导致扭曲嗜血杆菌对BZ抗性的原因。 [参考：36]

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