{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:45:49Z","timestamp":1789429549362,"version":"build-2803163510"},"reference-count":46,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T00:00:00Z","timestamp":1626998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European 451 Union\u2019s Horizon 2020 research and innovation program","award":["695596"],"award-info":[{"award-number":["695596"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Apicomplexan parasites are responsible for devastating diseases, including malaria, toxoplasmosis, and cryptosporidiosis. Current treatments are limited by emerging resistance to, as well as the high cost and toxicity of existing drugs. As obligate intracellular parasites, apicomplexans rely on the uptake of many essential metabolites from their host. Toxoplasma gondii, the causative agent of toxoplasmosis, is auxotrophic for several metabolites, including sugars (e.g., myo-inositol), amino acids (e.g., tyrosine), lipidic compounds and lipid precursors (cholesterol, choline), vitamins, cofactors (thiamine) and others. To date, only few apicomplexan metabolite transporters have been characterized and assigned a substrate. Here, we set out to investigate whether untargeted metabolomics can be used to identify the substrate of an uncharacterized transporter. Based on existing genome- and proteome-wide datasets, we have identified an essential plasma membrane transporter of the major facilitator superfamily in T. gondii\u2014previously termed TgApiAT6-1. Using an inducible system based on RNA degradation, TgApiAT6-1 was depleted, and the mutant parasite\u2019s metabolome was compared to that of non-depleted parasites. The most significantly reduced metabolite in parasites depleted in TgApiAT6-1 was identified as the amino acid lysine, for which T. gondii is predicted to be auxotrophic. Using stable isotope-labeled amino acids, we confirmed that TgApiAT6-1 is required for efficient lysine uptake. Our findings highlight untargeted metabolomics as a powerful tool to identify the substrate of orphan transporters.<\/jats:p>","DOI":"10.3390\/metabo11080476","type":"journal-article","created":{"date-parts":[[2021,7,25]],"date-time":"2021-07-25T22:07:00Z","timestamp":1627250820000},"page":"476","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Untargeted Metabolomics Uncovers the Essential Lysine Transporter in Toxoplasma gondii"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6366-8599","authenticated-orcid":false,"given":"Joachim","family":"Kloehn","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Medicine, University of Geneva, CMU, Rue Michel-Servet 1, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Lunghi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Medicine, University of Geneva, CMU, Rue Michel-Servet 1, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6584-9756","authenticated-orcid":false,"given":"Emmanuel","family":"Varesio","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences of Western Switzerland, School of Pharmaceutical Sciences, Mass Spectrometry Core Facility (MZ 2.0), University of Geneva, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Dubois","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Medicine, University of Geneva, CMU, Rue Michel-Servet 1, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4156-2109","authenticated-orcid":false,"given":"Dominique","family":"Soldati-Favre","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Medicine, University of Geneva, CMU, Rue Michel-Servet 1, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Flegr, J., Prandota, J., Sovickova, M., and Israili, Z.H. 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