Snábel V, DeMeeŵs T, Várady M, Nansen P, Bjørn H, Corba J
Danish Center for Experimental Parasitology, The Royal Veterinary and Agricultural University, Frederiksberg.
Parasitol Res. 2000 Jun;86(6):486-90. doi: 10.1007/s004360050698.
Information about genetic changes during the selection process could indicate mechanisms underlying the spread of resistance to anthelmintic drugs. For clarification of the role of the Mpi locus encoding mannose-phosphate isomerase enzyme in determining resistance, genotyping of Oesophagostomum dentatum strains was performed using an isoelectrofocusing technique. In levamisole- and pyrantel-selected strains the allele associated with resistance has probably been found. Significant values for genetic differentiation between treated and untreated strains of common origin were recorded by F(st) indices (theta = 0.078; P = 0.0008). The specific genomic makeup of a flubendazole-resistant strain, which did not correlate with that of the remaining isolates, might be ascribed to a different action of the anthelmintic or different environmental conditions under which resistance against this drug arose. The absence of heterozygotes in male populations indicated an XX/X0 system of sex determination for the Mpi locus, thus providing a greater potential for the development of resistance. A possible involvement of alleles linked with mannose-phosphate isomerase in alterations of membrane receptors that can be associated with resistance against imidothiazole-based drugs is discussed.
关于选择过程中基因变化的信息可以揭示抗驱虫药耐药性传播的潜在机制。为了阐明编码甘露糖磷酸异构酶的Mpi基因座在决定耐药性中的作用,使用等电聚焦技术对齿食道口线虫菌株进行了基因分型。在左旋咪唑和噻嘧啶选择的菌株中,可能已经发现了与耐药性相关的等位基因。通过F(st)指数记录了来自共同起源的处理菌株和未处理菌株之间显著的遗传分化值(theta = 0.078;P = 0.0008)。一种氟苯达唑耐药菌株的特定基因组组成与其余分离株不相关,这可能归因于驱虫药的不同作用或产生这种药物耐药性的不同环境条件。雄性群体中杂合子的缺失表明Mpi基因座的性别决定系统为XX/X0,因此具有更大的耐药性发展潜力。本文还讨论了与甘露糖磷酸异构酶相关的等位基因可能参与膜受体改变,而这种改变可能与对基于咪唑噻唑的药物的耐药性有关。