{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T20:47:51Z","timestamp":1776890871237,"version":"3.51.2"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009067","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T00:00:00Z","timestamp":1611100800000}}],"reference-count":91,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T00:00:00Z","timestamp":1609372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Brazilian National Research Council","award":["245823\/2012-3"],"award-info":[{"award-number":["245823\/2012-3"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI060767"],"award-info":[{"award-number":["AI060767"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Inorganic ions such as phosphate, are essential nutrients required for a broad spectrum of cellular functions and regulation. During infection, pathogens must obtain inorganic phosphate (P<jats:sub>i<\/jats:sub>) from the host. Despite the essentiality of phosphate for all forms of life, how the intracellular parasite <jats:italic>Toxoplasma gondii<\/jats:italic> acquires P<jats:sub>i<\/jats:sub> from the host cell is still unknown. In this study, we demonstrated that <jats:italic>Toxoplasma<\/jats:italic> actively internalizes exogenous P<jats:sub>i<\/jats:sub> by exploiting a gradient of Na<jats:sup>+<\/jats:sup> ions to drive P<jats:sub>i<\/jats:sub> uptake across the plasma membrane. The Na<jats:sup>+<\/jats:sup>-dependent phosphate transport mechanism is electrogenic and functionally coupled to a cipargarmin sensitive Na<jats:sup>+<\/jats:sup>-H<jats:sup>+<\/jats:sup>-ATPase. <jats:italic>Toxoplasma<\/jats:italic> expresses one transmembrane P<jats:sub>i<\/jats:sub> transporter harboring PHO4 binding domains that typify the PiT Family. This transporter named TgPiT, localizes to the plasma membrane, the inward buds of the endosomal organelles termed VAC, and many cytoplasmic vesicles. Upon P<jats:sub>i<\/jats:sub> limitation in the medium, TgPiT is more abundant at the plasma membrane. We genetically ablated the <jats:italic>PiT<\/jats:italic> gene, and \u0394TgPiT parasites are impaired in importing P<jats:sub>i<\/jats:sub> and synthesizing polyphosphates. Interestingly, \u0394TgPiT parasites accumulate 4-times more acidocalcisomes, storage organelles for phosphate molecules, as compared to parental parasites. In addition, these mutants have a reduced cell volume, enlarged VAC organelles, defects in calcium storage and a slightly alkaline pH. Overall, these mutants exhibit severe growth defects and have reduced acute virulence in mice. In survival mode, \u0394TgPiT parasites upregulate several genes, including those encoding enzymes that cleave or transfer phosphate groups from phosphometabolites, transporters and ions exchangers localized to VAC or acidocalcisomes. Taken together, these findings point to a critical role of TgPiT for P<jats:sub>i<\/jats:sub> supply for <jats:italic>Toxoplasma<\/jats:italic> and also for protection against osmotic stresses.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009067","type":"journal-article","created":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T23:13:29Z","timestamp":1609456409000},"page":"e1009067","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":17,"title":["A single Na+-Pi cotransporter in Toxoplasma plays key roles in phosphate import and control of parasite osmoregulation"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7503-418X","authenticated-orcid":true,"given":"Beejan","family":"Asady","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2251-6409","authenticated-orcid":true,"given":"Claudia 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D.","family":"Romano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5549-2362","authenticated-orcid":true,"given":"Isabelle","family":"Coppens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2020,12,31]]},"reference":[{"key":"ppat.1009067.ref001","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1002\/bies.950120804","article-title":"From cell membrane to nucleotides: the phosphate regulon in Escherichia coli","volume":"12","author":"A Torriani","year":"1990","journal-title":"Bioessays"},{"key":"ppat.1009067.ref002","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1271\/bbb.66.790","article-title":"Gene expression during Pi deficiency in Pholiota nameko: accumulation of mRNAs for two transporters","volume":"66","author":"Y Tasaki","year":"2002","journal-title":"Biosci Biotechnol 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