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bioRxiv · 10.1101/2025.04.17.649150

ZFT is the major iron and zinc transporter in Toxoplasma gondii

Aghabi, D.·Gallego Rubio, C.·Cortijo Martinez, M.·Pouzache, A.·Gibson, E. J.·Pagura, L.·Harding, C. R.
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Abstract

Transition metals, such as iron and zinc, are indispensable trace elements for eukaryotic life, acting as co-factors in essential processes ranging from metabolism to DNA replication. These metals can be transported into cells by an evolutionary-conserved family of metal transporters; however, how the ubiquitous mammalian parasite Toxoplasma gondii acquires essential metals has been unknown. Here, we have identified and characterised the first iron and zinc importer in T. gondii. This transporter, named ZFT, localised to the parasite plasma membrane and is essential for the parasites life cycle. We find ZFT is regulated by iron availability and overexpression sensitises cells to excess iron and zinc. Using a conditional knockdown system, we find that knockdown of ZFT leads to reduction in mitochondrial respiration and a switch to a more quiescent lifecycle stage. To confirm transport activity, we find that knockdown of ZFT leads to a reduction is parasite-associated zinc and iron, and ZFT expression complements loss of zinc transporter activity in a yeast model. Further, expression of ZFT in Xenopus oocytes demonstrates direct uptake of iron, which outcompeted in the presence of zinc. Overall, we have identified the first metal uptake transporter in T. gondii and demonstrated the importance of iron and zinc to the parasite. This finding advances our understanding how this obligate intracellular parasite acquires nutrients from its host.

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Aghabi, D., Gallego Rubio, C., Cortijo Martinez, M., Pouzache, A., Gibson, E. J., Pagura, L., Harding, C. R.. 2025-04-17. ZFT is the major iron and zinc transporter in Toxoplasma gondii. https://doi.org/10.1101/2025.04.17.649150

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