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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Virulence differences in Toxoplasma mediated by amplification of a family of polymorphic pseudokinases
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Virulence differences in Toxoplasma mediated by amplification of a family of polymorphic pseudokinases

机译：一个多态性假激酶家族的扩增介导的弓形虫毒力差异

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摘要

The population structure of Toxoplasma gondii includes three highly prevalent clonal lineages referred to as types I, II, and III, which differ greatly in virulence in the mouse model. Previous studies have implicated a family of serine/threonine protein kinases found in rhoptries (ROPs) as important in mediating virulence differences between strain types. Here, we explored the genetic basis of differences in virulence between the highly virulent type I lineage and moderately virulent type II based on successful genetic cross between these lineages. Genome-wide association revealed that a single quantitative trait locus controls the dramatic difference in lethality between these strain types. Neither R0P16 nor R0P18, previously implicated in virulence of T. gondii, was found to contribute to differences between types I and II. Instead, the major virulence locus contained a tandem cluster of polymorphic alleles of R0P5, which showed similar protein expression between strains. ROP5 contains a conserved serine/threonine protein kinase domain that includes only part of the catalytic triad, and hence, all members are considered to be pseudokinases. Genetic disruption of the entire ROPS locus in the type I lineage led to complete attenuation of acute virulence, and complementation with ROPS restored lethality to WT levels. These findings reveal that a locus of polymorphic pseudokinases plays an important role in pathogene-sis of toxoplasmosis in the mouse model.
机译：弓形虫的种群结构包括三个高度流行的克隆谱系，称为I，II和III型，它们在小鼠模型中的毒力差异很大。先前的研究已经暗示，在rhoptries（ROP）中发现的丝氨酸/苏氨酸蛋白激酶家族对于介导菌株类型之间的毒力差异很重要。在这里，我们基于这些谱系之间成功的遗传杂交，探索了高毒性的I型谱系和中等毒性的II型谱系之间毒力差异的遗传基础。全基因组关联揭示，单个数量性状基因座控制了这些菌株类型之间致死率的巨大差异。以前与刚地弓形虫的毒力有关的R0P16和R0P18均未发现会导致I型和II型之间的差异。相反，主要毒力基因座包含R0P5多态性等位基因的串联簇，在菌株之间显示相似的蛋白表达。 ROP5包含一个保守的丝氨酸/苏氨酸蛋白激酶结构域，该结构域仅包含催化三联体的一部分，因此，所有成员均被视为假激酶。 I型谱系中整个ROPS基因座的遗传破坏导致急性毒力完全减弱，与ROPS的互补将致死力恢复至WT水平。这些发现表明，在小鼠模型中，多态性假激酶基因座在弓形虫病的发病中起着重要作用。

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  • 作者

    Michael S. Behnke; Asis Khan; John C. Wootton; Jitender P. Dubey; Keliang Tang; L. David Sibley;

  • 作者单位

    Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110;

    Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110;

    Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894;

    Animal Parasitic Disease Laboratory,Animal and Natural Resources Institute, Agricultural Research Service, US Department of Agriculture, Beltsville, MD 20705;

    Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110;

    Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    copy-number variation; parasite; quantitative trait locus mapping; genetic mapping;

    机译：拷贝数变化;寄生虫数量性状基因座定位基因作图;

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