ZFT is the major iron and zinc transporter in Toxoplasma gondii

Transition metals, such as iron and zinc, are indispensable trace elements for eukaryotic life, acting as co-factors in essential processes ranging from respiration and 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 acquired 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 parasite’s 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 a 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 complements loss of zinc transporter activity in a yeast model. Overall, we have identified the first metal uptake transporter in T. gondii and demonstrated the importance iron and zinc transport to the cell. This finding reveals a critical piece of the puzzle in understanding how this obligate intracellular parasite thrives within its host.