LPHI, University Montpellier, Inserm, CNRS, Montpellier, France.
Virulence. 2024 Dec;15(1):2329566. doi: 10.1080/21505594.2024.2329566. Epub 2024 Mar 20.
is an obligate intracellular parasite responsible for a pathology called toxoplasmosis, which primarily affects immunocompromised individuals and developing foetuses. The parasite can scavenge essential nutrients from its host to support its growth and survival. Among them, iron is one of the most important elements needed to sustain basic cellular functions as it is involved in a number of key metabolic processes, including oxygen transport, redox balance, and electron transport. We evaluated the effects of an iron chelator on the development of several parasite strains and found that they differed in their ability to tolerate iron depletion. The growth of parasites usually associated with a model of acute toxoplasmosis was strongly affected by iron depletion, whereas cystogenic strains were less sensitive as they were able to convert into persisting developmental forms that are associated with the chronic form of the disease. Ultrastructural and biochemical characterization of the impact of iron depletion on parasites also highlighted striking changes in both their metabolism and that of the host, with a marked accumulation of lipid droplets and perturbation of lipid homoeostasis. Overall, our study demonstrates that although acute iron depletion has an important effect on the growth of , it has a more profound impact on actively dividing parasites, whereas less metabolically active parasite forms may be able to avoid some of the most detrimental consequences.
是一种专性细胞内寄生虫,可引起一种名为弓形体病的病理学,主要影响免疫功能低下的个体和发育中的胎儿。寄生虫可以从宿主中掠夺必需的营养物质来支持其生长和存活。其中,铁是维持基本细胞功能所需的最重要元素之一,因为它参与了许多关键的代谢过程,包括氧气运输、氧化还原平衡和电子传递。我们评估了一种铁螯合剂对几种寄生虫株发育的影响,发现它们在耐受铁耗竭的能力上存在差异。与急性弓形体病模型相关的寄生虫生长受到铁耗竭的强烈影响,而囊虫株则不太敏感,因为它们能够转化为与疾病慢性形式相关的持续发育形式。铁耗竭对寄生虫的超微结构和生化特性的影响也突出了其代谢和宿主代谢的显著变化,脂质滴的明显积累和脂质稳态的扰动。总的来说,我们的研究表明,尽管急性铁耗竭对的生长有重要影响,但它对活跃分裂的寄生虫的影响更为深远,而代谢活性较低的寄生虫形式可能能够避免一些最不利的后果。