Laboratory assays reveal diverse phenotypes among microfilariae ofDirofilaria immitisisolates with known macrocyclic lactone susceptibility status
Laboratory assays reveal diverse phenotypes among microfilariae ofDirofilaria immitisisolates with known macrocyclic lactone susceptibility status
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DOI：
10.1371/journal.pone.0237150
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发表时间：
2020-08-06
期刊：
影响因子：
3.7
通讯作者：
Brewer, Matthew T.
中科院分区：
文献类型：
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作者：
Jesudoss Chelladurai, Jeba R. J.;Martin, Katy A.;Brewer, Matthew T.
预防犬心丝虫引起的犬心丝虫病依赖于大环内酯驱虫药的化学预防。令人担忧的是，有越来越多的d。具有对大环内酯耐药和突破预防能力的拟殖菌。然而，目前还没有一种完善的实验室检测方法可以利用微丝虫的生化表型来预测耐药状况。在这项研究中，我们评估了测量细胞通透性、代谢和p -糖蛋白介导的外排的实验室测定。我们的实验表明，台盼蓝、碘化丙啶染色和瑞祖啉代谢可以检测d。但这些方法都不能准确预测所有耐药菌株的药敏状况。p -糖蛋白分析表明，不同菌株的P-gp表达谱可能不同，研究不同P-gp基因之间的药理学差异是有必要的。需要进一步的研究来调查和优化实验室分析。当将细胞死亡测定法应用于线虫寄生虫的药物筛选研究时，应谨慎使用。
Prevention of canine heartworm disease caused byDirofilaria immitisrelies on chemoprophylaxis with macrocyclic lactone anthelmintics. Alarmingly, there are increased reports ofD.immitisisolates with resistance to macrocyclic lactones and the ability to break through prophylaxis. Yet, there is not a well-established laboratory assay that can utilize biochemical phenotypes of microfilariae to predict drug resistance status. In this study we evaluated laboratory assays measuring cell permeability, metabolism, and P-glycoprotein-mediated efflux. Our assays revealed that trypan blue, propidium iodide staining, and resazurin metabolism could detect differences amongD.immitisisolates but none of these approaches could accurately predict drug susceptibility status for all resistant isolates tested. P-glycoprotein assays suggested that the repertoire of P-gp expression is likely to vary among isolates, and investigation of pharmacological differences among different P-gp genes is warranted. Further research is needed to investigate and optimize laboratory assays forD.immitismicrofilariae, and caution should be applied when adapting cell death assays to drug screening studies for nematode parasites.