Live imaging of the Cryptosporidium parvum life cycle reveals direct development of male and female gametes from type I meronts.

Live imaging of the Cryptosporidium parvum life cycle reveals direct development of male and female gametes from type I meronts.
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DOI:
10.1371/journal.pbio.3001604
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发表时间:
2022-04
期刊:
影响因子:
9.8
通讯作者:
--
中科院分区:
生物学1区
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隐孢子虫是世界范围内与水媒暴发、社区传播或人畜共患传播有关的腹泻的主要传染原因。这种寄生虫对幼儿死亡率有重大影响,感染既是营养不良和发育迟缓的后果,也是其原因。目前没有疫苗,治疗选择也非常有限。隐孢子虫是顶复合体的一员,并且,作为这方面的典型,原生动物门依赖于无性和有性繁殖。与包括疟原虫在内的其他顶复合体不同,隐孢子虫的整个生命周期在一个宿主体内不到3天就能完成。在这里,我们建立了一个模型来描绘活细胞的生命周期进程,并观察、跟踪和比较无性期和有性期寄生虫的核分裂。我们建立了所有阶段细胞周期的长度和序列,并绘制了寄生虫在多轮入侵和退出中的发育命运图。我们认为寄生虫执行了一个内在的程序,即3代无性复制,然后是独立于环境刺激的单代性阶段。我们没有发现形态上不同的中间阶段(四倍体II型meront)的证据,但证明了8N型I型meront的配子直接发育。每一个meront的后代要么是无性的,要么是有性的,但重要的是,有性的meront会产生雄性和雌性。我们定义了一个隐孢子虫的生命周期,与Tyzzer的原始描述相匹配,与现在许多教科书中显示的球虫生命周期不一致。隐孢子虫是世界范围内引起腹泻的主要传染病。这项隐孢子虫发育的成像研究揭示了一种内在的无性和有性承诺和复制程序,需要修改目前大多数教科书中显示的这种重要寄生虫的生命周期。
Cryptosporidium is a leading infectious cause of diarrhea around the world associated with waterborne outbreaks, community spread, or zoonotic transmission. The parasite has significant impact on early childhood mortality, and infection is both a consequence and cause of malnutrition and stunting. There is currently no vaccine, and treatment options are very limited. Cryptosporidium is a member of the Apicomplexa, and, as typical for this, protist phylum relies on asexual and sexual reproduction. In contrast to other Apicomplexa, including the malaria parasite Plasmodium, the entire Cryptosporidium life cycle unfolds in a single host in less than 3 days. Here, we establish a model to image life cycle progression in living cells and observe, track, and compare nuclear division of asexual and sexual stage parasites. We establish the length and sequence of the cell cycles of all stages and map the developmental fate of parasites across multiple rounds of invasion and egress. We propose that the parasite executes an intrinsic program of 3 generations of asexual replication, followed by a single generation of sexual stages that is independent of environmental stimuli. We find no evidence for a morphologically distinct intermediate stage (the tetraploid type II meront) but demonstrate direct development of gametes from 8N type I meronts. The progeny of each meront is collectively committed to either asexual or sexual fate, but, importantly, meronts committed to sexual fate give rise to both males and females. We define a Cryptosporidium life cycle matching Tyzzer’s original description and inconsistent with the coccidian life cycle now shown in many textbooks. Cryptosporidium is a leading infectious cause of diarrhea around the world. This imaging study of Cryptosporidium development reveals an intrinsic program of asexual and sexual commitment and replication, requiring revision of the lifecycle currently shown in most textbooks for this important parasite.
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