Motility-dependent processes in Toxoplasma gondii tachyzoites and bradyzoites: same same but different.

IF 3.7 2区 生物学 Q2 MICROBIOLOGY
mSphere Pub Date : 2025-03-25 Epub Date: 2025-02-12 DOI:10.1128/msphere.00855-24
Robyn S Kent, Gary E Ward
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引用次数: 0

Abstract

During infection, Toxoplasma gondii tachyzoites must be able to move in order to migrate through tissues, cross biological barriers, and penetrate into and egress from cells they infect. Bradyzoite-stage parasites, which establish infection in naïve hosts, also require motility to escape from cysts after they are ingested and to subsequently migrate to the gut wall, where they either invade cells of the intestinal epithelium or squeeze between these cells to infect the underlying tissue. Little is known about the motility of bradyzoites, which we analyze in detail here and compare to the well-characterized motility and motility-dependent processes of tachyzoites. Unexpectedly, bradyzoites were found to be as motile as tachyzoites in a three-dimensional model extracellular matrix, and they showed increased invasion into and transmigration across monolayers of certain cell types, consistent with their need to establish infection in the gut. The motility of the two stages was inhibited to the same extent by cytochalasin D and KNX-002, compounds known to target the parasite's actomyosin-based motor. Other compounds that impact tachyzoite motility (tachyplegin and enhancer 5) have a reduced effect on bradyzoites. Furthermore, rapid bradyzoite egress from infected cells is not triggered by treatment with calcium ionophores, as it is with tachyzoites. The similarities and differences between these two life cycle stages highlight the need to characterize both tachyzoites and bradyzoites for a more complete understanding of the role of motility in the parasite life cycle and the effect that motility-targeting therapeutics will have on disease establishment and progression.

Importance: Toxoplasma gondii is a parasite that chronically infects around one-third of the world's population. Toxoplasma uses motility for multiple purposes during infection, including extracellular migration, invasion into host cells, and host cell egress. These motility-dependent processes have been extensively studied in the life cycle stage responsible for acute infection, the tachyzoite. In contrast, motility and motility-dependent processes are poorly understood in bradyzoite-stage parasites, which are responsible for both establishing infection after consumption of infected meat and initiating potentially life-threatening reactivated infections in the brains of immunocompromised individuals. We show here that the motility and motility-dependent processes of bradyzoites are similar in many respects to those of tachyzoites but markedly different in others. The results of this study highlight the need to consider both life cycle stages in attempts to develop drugs targeting parasite motility and the signaling processes that regulate motility-dependent processes during infection by these important human pathogens.

刚地弓形虫速殖子和慢殖子的运动依赖过程:相同,相同但不同。
在感染期间,刚地弓形虫速殖子必须能够移动,以便在组织中迁移,跨越生物屏障,并穿透和离开它们感染的细胞。慢殖子期寄生虫,在naïve宿主中建立感染,也需要在它们被摄入后从囊肿中逃脱并随后迁移到肠壁,在那里它们要么侵入肠上皮细胞,要么挤在这些细胞之间感染下层组织。我们对慢殖子的运动性知之甚少,本文将对其进行详细分析,并与速生子的运动性和运动性依赖过程进行比较。出乎意料的是,在三维模型细胞外基质中,慢殖子被发现与快殖子一样具有运动性,并且它们表现出对某些细胞类型单层的入侵和迁移增加,这与它们在肠道中建立感染的需要一致。细胞松弛素D和KNX-002在相同程度上抑制了这两个阶段的运动,这两种化合物已知是针对寄生虫的肌动球蛋白为基础的运动。其他影响速殖子运动的化合物(速殖子蛋白和增强剂5)对慢殖子的影响较小。此外,从感染细胞中快速排出的慢殖子不像速殖子那样由钙离子载体处理触发。这两个生命周期阶段之间的异同突出表明,有必要对快殖子和慢殖子进行特征描述,以便更全面地了解运动在寄生虫生命周期中的作用,以及运动靶向治疗对疾病建立和进展的影响。重要性:刚地弓形虫是一种寄生虫,慢性感染世界上约三分之一的人口。弓形虫在感染过程中利用运动性有多种目的,包括细胞外迁移、侵入宿主细胞和宿主细胞出口。这些运动依赖的过程已经被广泛地研究在负责急性感染的生命周期阶段,速殖子。相比之下,人们对慢速子期寄生虫的运动和运动依赖过程知之甚少,它们在食用受感染的肉类后建立感染,并在免疫功能低下的个体的大脑中启动可能危及生命的再激活感染。我们在这里表明,缓殖子的运动性和运动性依赖过程在许多方面与速殖子相似,但在其他方面明显不同。这项研究的结果强调,在试图开发针对寄生虫运动的药物时,需要考虑两个生命周期阶段,以及在这些重要的人类病原体感染期间调节运动依赖过程的信号过程。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
mSphere
mSphere Immunology and Microbiology-Microbiology
CiteScore
8.50
自引率
2.10%
发文量
192
审稿时长
11 weeks
期刊介绍: mSphere™ is a multi-disciplinary open-access journal that will focus on rapid publication of fundamental contributions to our understanding of microbiology. Its scope will reflect the immense range of fields within the microbial sciences, creating new opportunities for researchers to share findings that are transforming our understanding of human health and disease, ecosystems, neuroscience, agriculture, energy production, climate change, evolution, biogeochemical cycling, and food and drug production. Submissions will be encouraged of all high-quality work that makes fundamental contributions to our understanding of microbiology. mSphere™ will provide streamlined decisions, while carrying on ASM''s tradition for rigorous peer review.
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