A Coccidia-Specific Phosphate Transporter Is Essential for the Growth of Toxoplasma gondii Parasites

Abstract

To grow and survive within host cells, Toxoplasma must scavenge necessary nutrients from hosts to support its parasitism. Transporters located in the plasma membrane of the parasites play critical roles in nutrient acquisition. Toxoplasma encodes a large number of transporters, but so far, only a few have been characterized.

The Role of Inorganic Phosphate Transporters in Highly Proliferative Cells: From Protozoan Parasites to Cancer Cells

“…The evolutionary history was inferred using the neighbour-joining method, as described in the legend of Figure 2 . The PHS family members (with their respective GenBank information) are as follows: LamPho89 from L. amazonensis (GenBank: LAMA_000460500 [ 21 ]); LiPho84 from L. infantum (GenBank: AFJ96967.1 [ 16 ]), LdPho84 from L. donovani (GenBank: Q01440.1 [ 20 ]), and PsPho84 from Phytomonas serpens (GenBank: CCW62503.1 [ 18 ]); TcPho84 from Trypanosoma cruzi (GenBank:XM_809326.1 [ 6 ]), TbHMIT from T. brucei (GenBank: Tb11.02.3020 [ 17 ]), putative PfPho84 from P. falciparum (GenBank: XP_001349558.1), and GdPho84 from Giardia duodenalis (GenBank: GL50803_5164 [ 27 ]); TgPT2 from Toxoplasma gondii (GenBank: TGGT1_235150 [ 28 ]); ScPho84 from Saccharomyces cerevisiae (GenBank: CAA89157.1 [ 52 ]); NcPho-5 from Neurospora crassa (GenBank: AAA74899.1 [ 103 ]), AcPiT from Acanthamoeba castellanii (GenBank: ACA1_360390 [ 24 ]), and AcPiT2 and AcPiT3 from A. castellanii (GenBank: ACA1_341100 and ACA1_131460, respectively [ 26 ]); SLC22A1 from humans (GenBank: O15245 [ 97 ]); and SLC22A8 from humans (GenBank: Q8TCC7 [ 97 ]). Outgroup: human hGAPDH (GenBank: NP_002037.2).…”

“…TgPT2 depletion prevents Toxoplasma from growing by lowering the parasite fitness. Although TgPT2 depletion decreased parasite motility and invasion effectiveness, it did not affect the ability of parasites to escape from HFF cells [ 28 ]. TgPT2 displayed higher Pi transport activity at an acidic pH, implying that H 2 PO 4 -2 is the preferred substrate or that the transporting activity is H + -dependent ( Figure 5 ).…”

“…TgPT2 displayed higher Pi transport activity at an acidic pH, implying that H 2 PO 4 -2 is the preferred substrate or that the transporting activity is H + -dependent ( Figure 5 ). Moreover, Pi import was not completely blocked by the silencing of either TgPiT or TgPT2, indicating that both proteins were involved in Pi absorption by the parasite [ 28 ].…”

“…Pi uptake through the plasma membrane is the starting point for this anion, and it is essential for cell proliferation and for maintaining Pi homeostasis, which is already well-established for several organisms, including mammalian cells, bacteria, yeast, and plants [ 13 ]. Additionally, many studies and recent reports have attributed the importance of Pi transport to the support it proves for the proliferation of many types of protozoa and cancer cells [ 5 , 6 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ] ( Figure 1 ). Anionic Pi does not accumulate in the cytosol through simple diffusion across the cell membrane due to its negative electrochemical potential.…”