Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
Department of Cell and Developmental Biology, Biozentrum, University of Würzburg, Germany.
mBio. 2023 Apr 25;14(2):e0355622. doi: 10.1128/mbio.03556-22. Epub 2023 Feb 22.
Throughout its complex life cycle, the uniflagellate parasitic protist, Trypanosoma cruzi, adapts to different host environments by transitioning between elongated motile extracellular stages and a nonmotile intracellular amastigote stage that replicates in the cytoplasm of mammalian host cells. Intracellular T. cruzi amastigotes retain a short flagellum that extends beyond the opening of the flagellar pocket with access to the extracellular milieu. Contrary to the long-held view that the T. cruzi amastigote flagellum is inert, we report that this organelle is motile and displays quasiperiodic beating inside mammalian host cells. Kymograph analysis determined an average flagellar beat frequency of ~0.7 Hz for intracellular amastigotes and similar beat frequencies for extracellular amastigotes following their isolation from host cells. Inhibitor studies reveal that flagellar motility in T. cruzi amastigotes is critically dependent on parasite mitochondrial oxidative phosphorylation. These novel observations reveal that flagellar motility is an intrinsic property of T. cruzi amastigotes and suggest that this organelle may play an active role in the parasite infection process. Understanding the interplay between intracellular pathogens and their hosts is vital to the development of new treatments and preventive strategies. The intracellular "amastigote" stage of the Chagas disease parasite, Trypanosoma cruzi, is a critical but understudied parasitic life stage. Previous work established that cytosolically localized T. cruzi amastigotes engage physically and selectively with host mitochondria using their short, single flagellum. The current study was initiated to examine the dynamics of the parasite flagellum-host mitochondrial interaction through live confocal imaging and led to the unexpected discovery that the T. cruzi amastigote flagellum is motile.
在其复杂的生命周期中，无鞭毛寄生原生动物克氏锥虫通过在伸长的运动细胞外阶段和非运动的细胞内阿米巴阶段之间转换，适应不同的宿主环境，在细胞质中复制。细胞内的克氏锥虫阿米巴保留了一个短鞭毛，该鞭毛延伸超出鞭毛囊的开口，可进入细胞外环境。与长期以来认为克氏锥虫阿米巴鞭毛是惰性的观点相反，我们报告称，该细胞器是运动的，并在哺乳动物宿主细胞内表现出准周期性拍打。动态分析确定细胞内阿米巴的平均鞭毛拍打频率约为 0.7 Hz，从宿主细胞中分离出的细胞外阿米巴也具有类似的拍打频率。抑制剂研究表明，克氏锥虫阿米巴鞭毛的运动严重依赖寄生虫线粒体氧化磷酸化。这些新的观察结果表明，鞭毛运动是克氏锥虫阿米巴的固有特性，并表明该细胞器可能在寄生虫感染过程中发挥积极作用。 了解细胞内病原体与其宿主之间的相互作用对于开发新的治疗方法和预防策略至关重要。恰加斯病寄生虫克氏锥虫的细胞内“阿米巴”阶段是一个关键但研究不足的寄生生活阶段。以前的工作已经确定，细胞质定位的克氏锥虫阿米巴使用其短的单个鞭毛与宿主线粒体进行物理和选择性接触。目前的研究旨在通过活共聚焦成像检查寄生虫鞭毛与宿主线粒体相互作用的动力学，导致了一个意外的发现，即克氏锥虫阿米巴鞭毛是运动的。
