P-glycoprotein-like protein, a possible genetic marker for ivermectin resistance selection in Onchocerca volvulus
P-glycoprotein-like protein, a possible genetic marker for ivermectin resistance selection in Onchocerca volvulus
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DOI：
10.1016/j.molbiopara.2007.11.017
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发表时间：
2008-04-01
影响因子：
1.5
通讯作者：
Prichard, Roger K.
中科院分区：
文献类型：
--
作者：
Bourguinat, Catherine;Ardelli, Bernadette F.;Prichard, Roger K.
伊维菌素是大规模治疗盘尾丝虫病的唯一安全药物。据报道，动物胃肠道线虫寄生虫对IVM具有耐药性。扭转盘尾丝虫病对IVM反应的减少可能对盘尾丝虫病控制规划产生重大影响。我们已经发现证据表明，在O. volvulus中，重复IVM处理选择了p -糖蛋白样蛋白（PLP）的特定等位基因，这是一种半大小的ABC转运蛋白。在这项研究中，回旋弧菌样本来自喀麦隆的一项临床试验，在该试验中，患者在IVM治疗前和治疗后3年（1994-1997）取样。4个处理组：150 μ g/kg （1 × p.a.或4 × p.a.）和800 μ g/kg （1 × p.a.或4 × p.a.）。对大丝虫的PLP基因和两个对照基因进行了476 bp的基因分型。在PLP扩增子中发现的6个多态性位点中，有3个位点经4次p.a. IVM处理后（共13次IVM处理）在雌虫中表现出显著的选择性，其中一个相同的单核苷酸多态性（SNPs）在雄虫中表现出显著的选择性。在雌性蠕虫中选择的一个snp引起了假定的蛋白质序列的氨基酸编码变化。我们发现了一些基因型的明确选择，高snp关联和多态性丢失在4 x p.a. IVM治疗后。这些PLP snp和基因型可作为田间IVM抗性选择的有用标记。(c) 2007 Elsevier B.V.版权所有
Ivermectin (IVM) is the only safe drug for mass-treatment of onchocerciasis. IVM resistance has been reported in gastrointestinal nematode parasites of animals. A reduction in response to IVM in Onchocerca volvulus could have significant consequences for the onchocerciasis control programs. We have found evidence that, in O. volvulus, repeated IVM treatment selects for specific alleles, of P-glycoprotein-like protein (PLP), a half-sized ABC transporter. In this study, O. volvulus samples were derived from a clinical trial in Cameroon, in which patients were sampled before, and following 3 years (1994-1997) of IVM treatments. There were four treatment groups: 150 mu g/kg (1 x p.a. or 4 x p.a.) and 800 mu g/kg (1 x p.a. or 4 x p.a.). DNA of O. volvulus macrofilariae was genotyped over a 476 bp region of the PLP gene and at two control genes. Of the six polymorphic positions found in the PLP amplicon, three of them showed significant selection after 4 x p.a. treatment with IVM (total of 13 IVM treatments) in female worms, and one of the same single nucleotide polymorphisms (SNPs) showed significant selection in the male worms. One of the selected SNPs in the female worms caused an amino acid coding change in the putative protein sequence. We found a clear selection of some genotypes, a high SNPs association and a loss of polymorphism following 4 x p. a. treatment with IVM. These PLP SNPs and genotypes could be useful markers to follow selection for IVM resistance in the field. (c) 2007 Elsevier B.V. All rights reserved.