转基因表达的副蛔虫P-糖蛋白-11可调节秀丽隐杆线虫对伊维菌素的敏感性。
Transgenically expressed Parascaris P-glycoprotein-11 can modulate ivermectin susceptibility in Caenorhabditis elegans.
作者信息
Janssen I Jana I, Krücken Jürgen, Demeler Janina, von Samson-Himmelstjerna Georg
机构信息
Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163 Berlin, Germany.
出版信息
Int J Parasitol Drugs Drug Resist. 2015 Apr 8;5(2):44-7. doi: 10.1016/j.ijpddr.2015.03.003. eCollection 2015 Aug.
P-glycoproteins (Pgps) are suspected to mediate drug extrusion in nematodes contributing to macrocyclic lactone resistance. This association was recently shown for Parascaris Pgp-11. Ivermectin resistance was correlated with the presence of three pgp-11 single nucleotide polymorphisms and/or increased pgp-11 mRNA levels. In the present study, the ability of Pgp-11 to modulate ivermectin susceptibility was investigated by its expression in a pgp-11-deficient Caenorhabditis elegans strain. Expression of Parascaris pgp-11 in two transgenic lines significantly decreased ivermectin susceptibility in a motility (thrashing) assay conducted in liquid medium. The EC50 values increased by 3.2- and 4.6-fold in the two lines relative to a transgenic control strain. This is the first report on the successful functional analysis of a parasitic nematode Pgp in the model organism C. elegans.
P-糖蛋白（Pgps）被怀疑在介导线虫体内药物外排中发挥作用，从而导致对线虫大环内酯类药物产生抗性。最近在副蛔虫Pgp-11中发现了这种关联。伊维菌素抗性与三个pgp-11单核苷酸多态性的存在和/或pgp-11 mRNA水平升高相关。在本研究中，通过在缺乏pgp-11的秀丽隐杆线虫菌株中表达Pgp-11，研究了其调节伊维菌素敏感性的能力。在液体培养基中进行的运动（摆动）试验中，两个转基因品系中副蛔虫pgp-11的表达显著降低了伊维菌素敏感性。相对于转基因对照菌株，这两个品系的半数有效浓度（EC50）值分别增加了3.2倍和4.6倍。这是关于在模式生物秀丽隐杆线虫中成功对寄生线虫Pgp进行功能分析的首次报道。
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