Bartley Kathryn, Wright Harry W, Bull Robert S, Huntley John F, Nisbet Alasdair J
Moredun Research Institute, International Research Centre, Pentlands Science Park, Bush Loan, Penicuik, Midlothian, EH26 0PZ, UK.
Parasit Vectors. 2015 Jun 26;8:350. doi: 10.1186/s13071-015-0960-9.
Glutathione S-transferases (GSTs) facilitate detoxification of drugs by catalysing the conjugation of the reduced glutathione (GSH) to electrophilic xenobiotic substrates and therefore have a function in multi-drug resistance. As a result, knowledge of GSTs can inform both drug resistance in, and novel interventions for, the control of endo- and ectoparasite species. Acaricide resistance and the need for novel control methods are both pressing needs for Dermanyssus gallinae, a highly economically important haematophagous ectoparasite of poultry.
A transcriptomic database representing D. gallinae was examined and 11 contig sequences were identified with GST BlastX identities. The transcripts represented by 3 contigs, designated Deg-GST-1, -2 and -3, were fully sequenced and further characterized by phylogenetic analysis. Recombinant versions of Deg-GST-1, -2 and -3 (rDeg-GST) were enzymically active and acaricide-binding properties of the rDeg-GSTs were established by evaluating the ability of selected acaricides to inhibit the enzymatic activity of rDeg-GSTs.
6 of the identified GSTs belonged to the mu class, followed by 3 kappa, 1 omega and 1 delta class molecules. Deg-GST-1 and -3 clearly partitioned with orthologous mu class GSTs and Deg-GST-2 partitioned with delta class GSTs. Phoxim, permethrin and abamectin significantly inhibited rDeg-GST-1 activity by 56, 35 and 17% respectively. Phoxim also inhibited rDeg-2-GST (14.8%) and rDeg-GST-3 (20.6%) activities.
Deg-GSTs may have important roles in the detoxification of pesticides and, with the increased occurrence of acaricide resistance in this species worldwide, Deg-GSTs are attractive targets for novel interventions.
谷胱甘肽S-转移酶（GSTs）通过催化还原型谷胱甘肽（GSH）与亲电子异生物质底物的结合来促进药物解毒，因此在多药耐药中发挥作用。因此，了解GSTs有助于了解体内和体外寄生虫物种的耐药性以及新的干预措施。杀螨剂抗性和新型控制方法的需求对于家鸡皮刺螨（Dermanyssus gallinae）来说都是迫切需求，家鸡皮刺螨是一种对家禽具有高度经济重要性的吸血体外寄生虫。
检查了一个代表家鸡皮刺螨的转录组数据库，并通过GST BlastX同源性鉴定了11个重叠群序列。对由3个重叠群（命名为Deg-GST-1、-2和-3）代表的转录本进行了全序列测定，并通过系统发育分析进一步表征。Deg-GST-1、-2和-3（rDeg-GST）的重组版本具有酶活性，通过评估所选杀螨剂抑制rDeg-GSTs酶活性的能力来确定rDeg-GSTs的杀螨剂结合特性。
鉴定出的GSTs中有6个属于μ类，其次是3个κ类、1个ω类和1个δ类分子。Deg-GST-1和-3与直系同源的μ类GSTs明显聚类，Deg-GST-2与δ类GSTs聚类。辛硫磷、氯菊酯和阿维菌素分别显著抑制rDeg-GST-1活性56%、35%和17%。辛硫磷还抑制rDeg-2-GST（14.8%）和rDeg-GST-3（20.6%）的活性。
Deg-GSTs可能在农药解毒中发挥重要作用，并且随着全球该物种杀螨剂抗性的增加，Deg-GSTs是新型干预措施的有吸引力的靶点。
