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Here we report the first comprehensive investigation into purine and pyrimidine uptake by <jats:italic>T. vaginalis<\/jats:italic>. Multiple carriers were identified and characterized with regard to substrate selectivity and affinity. For nucleobases, a high\u2010affinity adenine transporter, a possible guanine transporter and a low affinity uracil transporter were found. Nucleoside transporters included two high affinity adenosine\/guanosine\/uridine\/cytidine transporters distinguished by different affinities to inosine, a lower affinity adenosine transporter, and a thymidine transporter. Nine Equilibrative Nucleoside Transporter (ENT) genes were identified in the <jats:italic>T. vaginalis<\/jats:italic> genome. All were expressed equally in metronidazole\u2010resistant and \u2010sensitive strains. Only TvagENT2 was significantly upregulated in the presence of extracellular purines; expression was not affected by co\u2010culture with human cervical epithelial cells. All TvagENTs were cloned and separately expressed in <jats:italic>Trypanosoma brucei<\/jats:italic>. We identified the main broad specificity nucleoside carrier, with high affinity for uridine and cytidine as well as purine nucleosides including inosine, as TvagENT3. The in\u2010depth characterization of purine and pyrimidine transporters provides a critical foundation for the development of new anti\u2010trichomonal nucleoside analogues.<\/jats:p>","DOI":"10.1111\/mmi.14840","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T04:35:01Z","timestamp":1636086901000},"page":"1489-1511","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Comprehensive characterization of purine and pyrimidine transport activities in <i>Trichomonas vaginalis<\/i> and functional cloning of a trichomonad nucleoside transporter"],"prefix":"10.1111","volume":"116","author":[{"given":"Manal J.","family":"Natto","sequence":"first","affiliation":[{"name":"Institute of Infection, Immunity and Inflammation College of Medical Veterinary and Life Sciences University of Glasgow  Glasgow 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