ABSTRACT
Toxoplasma gondii 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 T. gondii, 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.
Acknowledgements
We thank J.F. Dubremetz, M.L. Dardé, P. Bradley, and M.J. Gubbels for providing strains and antibodies. We thank the MRI platform and the Electron Microscopy facility of the University of Montpellier for providing access to their microscopes. Lipidomic analyses were performed by the “MetaToul-Lipidomique” platform (I2MC, Inserm, Toulouse, France; MetaboHUB-ANR-11-INBS-0010).
Disclosure statement
No potential conflict of interest was reported by the author(s).
Data Availability statement
The authors confirm that the data supporting the findings of this study are available in the article and its supplementary materials.
Author contribution
SB designed the experiments, supervised the study, performed experiments, analysed the data, wrote the manuscript, and acquired funding. EAR, AJMM, YB, AG and LB performed experiments and analysed the data. All authors have read and agreed to the published version of the manuscript.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/21505594.2024.2329566