Absence of association between Pfnfs1 mutation and in vitro susceptibility to lumefantrine in Plasmodium falciparum

Weilin Zeng , Wei Zhao , Hao Wei , Yucheng Qin , Zheng Xiang , Yanrui Wu , Xi Chen , Yanmei Zhang , Hui Zhao , Mengxi Duan , Wenya Zhu , Kemin Sun , Yiman Wu , Tao Liang , Ye Mou , Cheng Liu , Xiuya Tang , Yaming Huang , Liwang Cui , Zhaoqing Yang
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Abstract

Artemether-lumefantrine (AL) is the most widely used antimalarial drug for treating uncomplicated falciparum malaria. This study evaluated whether the K65Q mutation in the Plasmodium falciparum cysteine desulfurase IscS (Pfnfs1) gene was associated with alternated susceptibility to lumefantrine using clinical parasite samples from Ghana and the China-Myanmar border area. Parasite isolates from the China-Myanmar border had significantly higher IC50 values to lumefantrine than parasites from Ghana. In addition, the K65 allele was significantly more prevalent in the Ghanaian parasites (34.5%) than in the China-Myanmar border samples (6.8%). However, no difference was observed in the lumefantrine IC50 value between the Pfnfs1 reference K65 allele and the non reference 65Q allele in parasites from the two regions. These data suggest that the Pfnfs1 K65Q mutation may not be a reliable marker for reduced susceptibility to lumefantrine.

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恶性疟原虫的 Pfnfs1 突变与体外对氟抗喹啉的敏感性之间没有关联
蒿甲醚-本芴醇(AL)是治疗无并发症恶性疟原虫疟疾最广泛使用的抗疟药物。本研究利用加纳和中缅边境地区的临床寄生虫样本,评估了恶性疟原虫半胱氨酸脱硫酶IscS(Pfnfs1)基因中的K65Q突变是否与蒿甲醚-本芴醇的交替敏感性有关。来自中缅边境地区的寄生虫分离株对氟苯蝶啶的 IC50 值明显高于来自加纳的寄生虫。此外,K65等位基因在加纳寄生虫中的流行率(34.5%)明显高于中缅边境样本(6.8%)。然而,在这两个地区的寄生虫中,Pfnfs1参考K65等位基因和非参考65Q等位基因的鲁班霉素IC50值没有差异。这些数据表明,Pfnfs1 K65Q突变可能不是对氟抗喹啉敏感性降低的可靠标记。
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来源期刊
CiteScore
7.90
自引率
7.50%
发文量
31
审稿时长
48 days
期刊介绍: The International Journal for Parasitology – Drugs and Drug Resistance is one of a series of specialist, open access journals launched by the International Journal for Parasitology. It publishes the results of original research in the area of anti-parasite drug identification, development and evaluation, and parasite drug resistance. The journal also covers research into natural products as anti-parasitic agents, and bioactive parasite products. Studies can be aimed at unicellular or multicellular parasites of human or veterinary importance.
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