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Localization studies using confocal microscopy, a surface biotinylation assay, and trypsin digestion after digitonin permeabilization suggested that ABCI3 presents a dual localization in both mitochondria and the plasma membrane. From studies using parasites with a single knockout of\n            <jats:italic>ABCI3<\/jats:italic>\n            (\n            <jats:italic>ABCI3<\/jats:italic>\n            <jats:sup>+\/\u2212<\/jats:sup>\n            ), we provide evidence that ABCI3 is directly involved in susceptibility to the trivalent form of antimony (SbIII) and metal ions. Attempts to obtain parasites with a double knockout of\n            <jats:italic>ABCI3<\/jats:italic>\n            were unsuccessful, suggesting that\n            <jats:italic>ABCI3<\/jats:italic>\n            could be an essential gene in\n            <jats:named-content content-type=\"genus-species\">L. major<\/jats:named-content>\n            .\n            <jats:italic>ABCI3<\/jats:italic>\n            <jats:sup>+\/\u2212<\/jats:sup>\n            promastigotes were 5-fold more resistant to Sb\n            <jats:sup>III<\/jats:sup>\n            than the wild type, while\n            <jats:italic>ABCI3<\/jats:italic>\n            <jats:sup>+\/\u2212<\/jats:sup>\n            amastigotes were approximately 2-fold more resistant to pentavalent antimony (Sb\n            <jats:sup>V<\/jats:sup>\n            ). This resistance phenotype was associated with decreased Sb\n            <jats:sup>III<\/jats:sup>\n            accumulation due to decreased Sb\n            <jats:sup>III<\/jats:sup>\n            uptake.\n            <jats:italic>ABCI3<\/jats:italic>\n            <jats:sup>+\/\u2212<\/jats:sup>\n            parasites presented higher ATP levels and generated less mitochondrial superoxide after Sb\n            <jats:sup>III<\/jats:sup>\n            incubation. Finally, we observed that\n            <jats:italic>ABCI3<\/jats:italic>\n            <jats:sup>+\/\u2212<\/jats:sup>\n            parasites showed a slightly higher infection capacity than wild-type and add-back\n            <jats:italic>ABCI3<\/jats:italic>\n            <jats:sup>+\/\u2212<\/jats:sup>\n            ::3\u00d7FABCI3 parasites; however, after 72 h the number of\n            <jats:italic>ABCI3<\/jats:italic>\n            <jats:sup>+\/\u2212<\/jats:sup>\n            intracellular parasites per macrophage increased significantly. Our results show that ABCI3 is responsible for Sb\n            <jats:sup>III<\/jats:sup>\n            transport inside mitochondria, where it contributes to enhancement of the general toxic effects caused by Sb\n            <jats:sup>III<\/jats:sup>\n            . To our knowledge, ABCI3 is the first ABC transporter which is involved in susceptibility toward antimony, conferring Sb\n            <jats:sup>III<\/jats:sup>\n            resistance to parasites when it is partially deleted.\n          <\/jats:p>","DOI":"10.1128\/aac.01115-17","type":"journal-article","created":{"date-parts":[[2017,10,3]],"date-time":"2017-10-03T00:30:26Z","timestamp":1506990626000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["ABCI3 Is a New Mitochondrial ABC Transporter from Leishmania major Involved in Susceptibility to Antimonials and Infectivity"],"prefix":"10.1128","volume":"61","author":[{"given":"Talia","family":"Arcari","sequence":"first","affiliation":[{"name":"Instituto de Parasitolog\u00eda y Biomedicina L\u00f3pez-Neyra, CSIC (IPBLN-CSIC), Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Ignacio","family":"Manzano","sequence":"additional","affiliation":[{"name":"Instituto de Parasitolog\u00eda y Biomedicina L\u00f3pez-Neyra, CSIC (IPBLN-CSIC), Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Gamarro","sequence":"additional","affiliation":[{"name":"Instituto de Parasitolog\u00eda y Biomedicina L\u00f3pez-Neyra, CSIC (IPBLN-CSIC), Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"unstructured":"World Health Organization. 2017. 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