The essential genome of Plasmodium knowlesi reveals determinants of antimalarial susceptibility

IF 45.8 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2025-02-06 DOI:10.1126/science.adq6241

Brendan Elsworth, Sida Ye, Sheena Dass, Jacob A. Tennessen, Qudseen Sultana, Basil T. Thommen, Aditya S. Paul, Usheer Kanjee, Christof Grüring, Marcelo U. Ferreira, Marc-Jan Gubbels, Kourosh Zarringhalam, Manoj T. Duraisingh

引用次数: 0

Abstract

Measures to combat the parasites that cause malaria have become compromised because of reliance on a small arsenal of drugs and emerging drug resistance. We conducted a transposon mutagenesis screen in the primate malaria parasite Plasmodium knowlesi , producing the most complete classification of gene essentiality in any Plasmodium spp. to date, with the resolution to define truncatable genes. We found conservation in the druggable genome between Plasmodium spp. and divergences in mitochondrial metabolism. Perturbation analyses with the frontline antimalarial artemisinin revealed modulators that both increase and decrease drug susceptibility. Our findings aid prioritization of drug and vaccine targets for the Plasmodium vivax clade and reveal mechanisms of resistance that can inform therapeutic development.

查看原文本刊更多论文

诺氏疟原虫的基本基因组揭示了抗疟疾敏感性的决定因素

由于依赖少量药物和正在出现的耐药性，抗击引起疟疾的寄生虫的措施已经受到损害。我们在灵长类疟疾寄生虫诺氏疟原虫中进行了转座突变筛选，产生了迄今为止所有疟原虫中最完整的基因必要性分类，并确定了可截断的基因。我们发现疟原虫可用药基因组的保守性和线粒体代谢的差异。对一线抗疟药物青蒿素的摄动分析揭示了可增加和降低药物敏感性的调节因子。我们的研究结果有助于确定间日疟原虫支系药物和疫苗靶点的优先级，并揭示耐药性机制，为治疗开发提供信息。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

期刊介绍： Science is a leading outlet for scientific news, commentary, and cutting-edge research. Through its print and online incarnations, Science reaches an estimated worldwide readership of more than one million. Science’s authorship is global too, and its articles consistently rank among the world's most cited research. Science serves as a forum for discussion of important issues related to the advancement of science by publishing material on which a consensus has been reached as well as including the presentation of minority or conflicting points of view. Accordingly, all articles published in Science—including editorials, news and comment, and book reviews—are signed and reflect the individual views of the authors and not official points of view adopted by AAAS or the institutions with which the authors are affiliated. Science seeks to publish those papers that are most influential in their fields or across fields and that will significantly advance scientific understanding. Selected papers should present novel and broadly important data, syntheses, or concepts. They should merit recognition by the wider scientific community and general public provided by publication in Science, beyond that provided by specialty journals. Science welcomes submissions from all fields of science and from any source. The editors are committed to the prompt evaluation and publication of submitted papers while upholding high standards that support reproducibility of published research. Science is published weekly; selected papers are published online ahead of print.