Natural variation in Caenorhabditis elegans responses to the anthelmintic emodepside.
Natural variation in Caenorhabditis elegans responses to the anthelmintic emodepside.
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DOI：
10.1016/j.ijpddr.2021.04.001
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Andersen EC
中科院分区：
文献类型：
--
作者：
Wit J;Rodriguez BC;Andersen EC
寄生线虫感染的治疗主要依赖于驱虫药的使用。然而，这种药物库是有限的，对大多数驱虫药的耐药性是普遍的。依地平是一种新型抗胃肠道线虫和丝虫的驱虫药。对其他驱虫药类耐药的线虫对依莫得甙敏感，表明依莫得甙的作用模式与以前的驱虫药不同。实验室适应的秀丽隐杆线虫N2株对依莫地昔敏感，遗传选择和体外实验表明，一个大的K+电导（BK）通道基因，在依莫地昔的作用模式。为了了解自然种群对emodepside的反应，我们测量了野生C。在暴露于药物后，elegans菌株发现了物种间的自然变异。在C. elegans emodepside反应与EST-I中的氨基酸取代相关，但除了EST-I编码变体之外的遗传机制可能是野生C. elegans菌株。此外，测定的菌株在低浓度的依莫地昔中具有更高的后代产量（激素效应）。我们发现，自然变异影响emodepside敏感性，支持C。elegans作为模型系统，研究天然线虫种群的emodepside反应。不同的C. elegans物种。野生型C.线虫模拟寄生虫emodepside反应的自然差异。依莫地昔酯靶点EST-I和其他基因座的变异与耐药性相关。低剂量的依莫地昔对后代产生激素效应。
Treatment of parasitic nematode infections depends primarily on the use of anthelmintics. However, this drug arsenal is limited, and resistance against most anthelmintics is widespread. Emodepside is a new anthelmintic drug effective against gastrointestinal and filarial nematodes. Nematodes that are resistant to other anthelmintic drug classes are susceptible to emodepside, indicating that the emodepside mode of action is distinct from previous anthelmintics. The laboratory-adapted Caenorhabditis elegans strain N2 is sensitive to emodepside, and genetic selection and in vitro experiments implicated slo-1, a large K+ conductance (BK) channel gene, in emodepside mode of action. In an effort to understand how natural populations will respond to emodepside, we measured brood sizes and developmental rates of wild C. elegans strains after exposure to the drug and found natural variation across the species. Some of the observed variation in C. elegans emodepside responses correlates with amino acid substitutions in slo-1, but genetic mechanisms other than slo-1 coding variants likely underlie emodepside resistance in wild C. elegans strains. Additionally, the assayed strains have higher offspring production in low concentrations of emodepside (a hormetic effect). We find that natural variation affects emodepside sensitivity, supporting the suitability of C. elegans as a model system to study emodepside responses across natural nematode populations. Emodepside responses vary across the C. elegans species. Wild strains of C. elegans model natural differences in parasite emodepside responses. Variation in the emodepside target slo-1 and other loci correlate with resistance. Low doses of emodepside cause a hormetic effect on offspring production.
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影响因子：
14.9
作者：
Cook, Daniel E.;Zdraljevic, Stefan;Andersen, Erik C.
通讯作者：
Andersen, Erik C.
影响因子：
2.6
作者：
Geary, TG;Thompson, DP
通讯作者：
Thompson, DP
影响因子：
2
作者：
Altreuther, G;Buch, J;Radeloff, I
通讯作者：
Radeloff, I
影响因子：
4.5
作者：
Evans KS;Zdraljevic S;Stevens L;Collins K;Tanny RE;Andersen EC
通讯作者：
Andersen EC
DOI：
10.1007/978-1-61779-867-2_3
发表时间：
2012
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Boyd, Windy A;Smith, Marjolein V;Freedman, Jonathan H
通讯作者：
Freedman, Jonathan H