Oxidative Phosphorylation Is Required for Powering Motility and Development of the Sleeping Sickness Parasite Trypanosoma brucei in the Tsetse Fly Vector.
Oxidative Phosphorylation Is Required for Powering Motility and Development of the Sleeping Sickness Parasite Trypanosoma brucei in the Tsetse Fly Vector.
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DOI：
10.1128/mbio.02357-21
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发表时间：
2022-02-22
期刊：
影响因子：
6.4
通讯作者：
Schnaufer A
中科院分区：
文献类型：
--
作者：
Dewar CE;Casas-Sanchez A;Dieme C;Crouzols A;Haines LR;Acosta-Serrano Á;Rotureau B;Schnaufer A
布鲁氏锥虫是一种单细胞寄生虫，通过噬血的采采蝇传播。从哺乳动物血流形态到采采中肠形态以及随后的感染性唾液腺形态的生命周期进展取决于复杂的发育步骤和不同苍蝇组织内的迁移。当寄生虫寄生在葡萄糖匮乏的昆虫中肠时，ATP的产生被认为依赖于通过氧化磷酸化（OXPHOS）激活线粒体氨基酸分解代谢。这一过程涉及呼吸链复合物和F1Fo-ATP合成酶，并需要这些复合物的蛋白质亚基，这些亚基编码在寄生虫的线粒体DNA （kDNA）中。在这里，我们发现kdna编码功能的逐渐丧失与采采蝇启动和完成发育的能力下降有关。首先，具有突变的F1Fo-ATP合酶的寄生虫，其OXPHOS能力降低，可以启动从血液到昆虫形态的分化，但它们不能在体外增殖。出乎意料的是，这些细胞仍然可以在采采中肠中定植。然而，这些寄生虫表现出运动性缺陷，在定植或迁移到后续采采组织时受到严重损害。其次，完全破坏F1Fo-ATP合成酶复合物的寄生虫，完全不能通过OXPHOS产生ATP，仍然可以在体外分化到第一昆虫阶段，但在体内几天内死亡，不能建立中肠感染。第三，完全缺乏kDNA的寄生虫可以开始分化，但很快就会死亡。综上所述，这些情况表明，通过OXPHOS高效产生ATP对于采采病媒的初始定植并不是必需的，但却需要为锥虫在蝇体内的迁移提供动力。
The single-celled parasite Trypanosoma brucei is transmitted by hematophagous tsetse flies. Life cycle progression from mammalian bloodstream form to tsetse midgut form and, subsequently, infective salivary gland form depends on complex developmental steps and migration within different fly tissues. As the parasite colonizes the glucose-poor insect midgut, ATP production is thought to depend on activation of mitochondrial amino acid catabolism via oxidative phosphorylation (OXPHOS). This process involves respiratory chain complexes and F1Fo-ATP synthase and requires protein subunits of these complexes that are encoded in the parasite's mitochondrial DNA (kDNA). Here, we show that progressive loss of kDNA-encoded functions correlates with a decreasing ability to initiate and complete development in the tsetse. First, parasites with a mutated F1Fo-ATP synthase with reduced capacity for OXPHOS can initiate differentiation from bloodstream to insect form, but they are unable to proliferate in vitro. Unexpectedly, these cells can still colonize the tsetse midgut. However, these parasites exhibit a motility defect and are severely impaired in colonizing or migrating to subsequent tsetse tissues. Second, parasites with a fully disrupted F1Fo-ATP synthase complex that is completely unable to produce ATP by OXPHOS can still differentiate to the first insect stage in vitro but die within a few days and cannot establish a midgut infection in vivo. Third, parasites lacking kDNA entirely can initiate differentiation but die soon after. Together, these scenarios suggest that efficient ATP production via OXPHOS is not essential for initial colonization of the tsetse vector but is required to power trypanosome migration within the fly.
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DOI：
10.1111/j.1432-1033.1987.tb13565.x
发表时间：
1987-08-03
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
CHRISTEN, R;GATTI, JL;BILLARD, R
通讯作者：
BILLARD, R
影响因子：
56.9
作者：
Asbury, CL;Fehr, AN;Block, SM
通讯作者：
Block, SM
DOI：
10.1111/j.1550-7408.1975.tb05210.x
发表时间：
1975-01-01
期刊：
JOURNAL OF PROTOZOOLOGY
影响因子：
--
作者：
BOHRINGER, S;HECKER, H
通讯作者：
HECKER, H
影响因子：
4.8
作者：
Bochud-Allemann, N;Schneider, A
通讯作者：
Schneider, A
影响因子：
11.4
作者：
CHEN, XJ;CLARKWALKER, GD
通讯作者：
CLARKWALKER, GD