# Transporters, an important but poorly studied area of Toxoplasma gondii

**Authors:** Liya Wang, Yujuan Jing, Jichao Yang, Xuke Yang, Jiahui Qian, Rui Fang, Fuchun Jian, Longxian Zhang, Senyang Li

PMC · DOI: 10.1186/s13071-025-07216-w · Parasites & Vectors · 2026-01-25

## TL;DR

This paper reviews the poorly understood transporters in Toxoplasma gondii, highlighting their roles in survival and metabolism, and proposes strategies to study them for potential therapeutic applications.

## Contribution

The paper proposes a novel screening strategy combining bioinformatics and CRISPR phenotyping to prioritize uncharacterized T. gondii transporters for functional study.

## Key findings

- Most T. gondii transporters remain poorly characterized despite their critical roles in survival and drug resistance.
- Recent advances in CRISPR-based screening and bioinformatics enable systematic identification of transporter candidates.
- Transporters are highlighted as potential therapeutic targets for Toxoplasma gondii.

## Abstract

Membrane transporters play a vital role in the obligate intracellular parasite Toxoplasma gondii, mediating the acquisition of nutrients from host cells, the regulation of ion gradients, and the maintenance of metabolic homeostasis. Despite their central importance for parasite survival, pathogenesis, and drug resistance, the majority of T. gondii transporters remain poorly characterized. Key unresolved questions include the mechanisms underlying purine nucleotide transport across the plasma membrane and the import/export of metabolites for core pathways in the apicoplast (e.g., thiamine, isopentenyl diphosphate[IPP]/dimethylallyl diphosphate [DMAPP], and coproporphyrinogen III) and mitochondria (e.g., amino acids and cofactors). Recent advances in bioinformatics and CRISPR-based phenotypic screening have enabled systematic identification of transporter candidates. This review summarizes current knowledge of T. gondii transporters localized to the plasma membrane, apicoplast, mitochondria, endoplasmic reticulum, and Golgi apparatus, highlighting their roles in nutrient acquisition, metabolic crosstalk, and organellar function. Furthermore, we propose a screening strategy integrating transmembrane domain prediction, CRISPR phenotyping, and hyperLOPIT-based protein localization to prioritize uncharacterized transporters for functional study. These insights underscore the potential of transporters as therapeutic targets and provide a roadmap for future research into the physiology of T. gondii.

The online version contains supplementary material available at 10.1186/s13071-025-07216-w.

## Linked entities

- **Chemicals:** isopentenyl diphosphate (PubChem CID 1195), dimethylallyl diphosphate (PubChem CID 647), coproporphyrinogen III (PubChem CID 321)
- **Species:** Toxoplasma gondii (taxon 5811)

## Full-text entities

- **Diseases:** pyruvate transporter deficiency (MESH:D015325), malaria (MESH:D008288), toxicity (MESH:D064420), cysts (MESH:D003560), growth impairment (MESH:D006130), N-linked and O-linked glycosylation (MESH:C567753), infection (MESH:D007239), iron (MESH:D000090463), zinc (MESH:C564286)
- **Chemicals:** alanine (MESH:D000409), palmitic acid (MESH:D019308), H+ (MESH:D006859), glycan (MESH:D011134), dephospho-coenzyme A (MESH:C015787), IPP (MESH:C004809), adenine (MESH:D000225), glyceraldehyde 3-phosphate (MESH:D005986), 32P] (MESH:C000615311), Asn (MESH:D001216), NADP+ (MESH:D009249), cytidine (MESH:D003562), TCA (MESH:D014233), mannose (MESH:D008358), polyphosphates (MESH:D011122), Heme (MESH:D006418), NAD+ (MESH:D009243), Acetyl-CoA (MESH:D000105), phospholipid (MESH:D010743), ornithine (MESH:D009952), 5-aminolevulinic acid (MESH:C000614854), cholesterol (MESH:D002784), oxygen (MESH:D010100), lysine (MESH:D008239), Carbohydrate (MESH:D002241), serine (MESH:D012694), CoA (MESH:D003065), purine nucleotide (MESH:D011685), myristate (MESH:D019814), ethanolamine (MESH:D019856), isoprenoid (MESH:D013729), pyrimidines (MESH:D011743), succinate (MESH:D019802), ATP (MESH:D000255), acyl-carnitine (MESH:C116917), nitrite (MESH:D009573), L-Tyr (MESH:D014443), AMP (MESH:D000249), monosaccharides (MESH:D009005), Arg (MESH:D001120), mevalonate (MESH:D008798), carbon (MESH:D002244), Inorganic phosphate (MESH:D010710), GDP (MESH:D006153), acetate (MESH:D000085), DHAP (MESH:D004099), inosine (MESH:D007288), allopurinol (MESH:D000493), sulfur (MESH:D013455), Fe-S (MESH:D007501), galactose (MESH:D005690), oligosaccharide (MESH:D009844), Lactate (MESH:D019344), thymidine (MESH:D013936), ceramide (MESH:D002518), biotin (MESH:D001710), citrate (MESH:D019343), alpha-ketoglutarate (MESH:D007656), zinc (MESH:D015032), 13C (MESH:C000615229)
- **Species:** Plasmodium berghei (species) [taxon 5821], Homo sapiens (human, species) [taxon 9606], Plasmodium falciparum (malaria parasite P. falciparum, species) [taxon 5833], Mus musculus (house mouse, species) [taxon 10090], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Escherichia coli (E. coli, species) [taxon 562], Coccidia (subclass) [taxon 5796], Toxoplasma gondii (species) [taxon 5811], Xenopus laevis (African clawed frog, species) [taxon 8355]
- **Mutations:** Gly107Ser, F37V

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12849547/full.md

## References

6 references — full list in the complete paper: https://tomesphere.com/paper/PMC12849547/full.md

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Source: https://tomesphere.com/paper/PMC12849547