{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:35:49Z","timestamp":1790908549823,"version":"4.1.0"},"reference-count":95,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,9,25]],"date-time":"2019-09-25T00:00:00Z","timestamp":1569369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100011011","name":"Junta de Andaluc\u00eda","doi-asserted-by":"publisher","award":["BIO1786"],"award-info":[{"award-number":["BIO1786"]}],"id":[{"id":"10.13039\/501100011011","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:p>\n                    Heme is an essential molecule synthetized through a broadly conserved 8\u2010step route that has been lost in trypanosomatid parasites. Interestingly,\n                    <jats:italic>Leishmania<\/jats:italic>\n                    reacquired by horizontal gene transfer from \u03b3\u2010proteobacteria the genes coding for the last 3 enzymes of the pathway. Here we show that intracellular amastigotes of\n                    <jats:italic>Leishmania major<\/jats:italic>\n                    can scavenge heme precursors from the host cell to fulfill their heme requirements, demonstrating the functionality of this partial pathway. To dissect its role throughout the\n                    <jats:italic>L. major<\/jats:italic>\n                    life cycle, the significance of\n                    <jats:italic>L. major<\/jats:italic>\n                    ferrochelatase (LmFeCH), the terminal enzyme of the route, was evaluated. LmFeCH expression in a heterologous system demonstrated its activity. Knockout promastigotes lacking\n                    <jats:italic>lmfech<\/jats:italic>\n                    were not able to use the ferrochelatase substrate protoporphyrin IX as a source of heme.\n                    <jats:italic>In vivo<\/jats:italic>\n                    infection of\n                    <jats:italic>Phlebotomus perniciosus<\/jats:italic>\n                    with knockout promastigotes shows that LmFeCH is not required for their development in the sandfly. In contrast, the replication of intracellular amastigotes was hampered\n                    <jats:italic>in vitro<\/jats:italic>\n                    by the deletion of\n                    <jats:italic>lmfech.<\/jats:italic>\n                    However,\n                    <jats:italic>\n                      LmFeCH\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    parasites produced disease in a cutaneous leishmaniasis murine model in a similar way as control parasites. Therefore, although\n                    <jats:italic>L. major<\/jats:italic>\n                    can synthesize\n                    <jats:italic>de novo<\/jats:italic>\n                    heme from macrophage precursors, this activity is dispensable being an unsuited target for leishmaniasis treatment.\u2014Orrego, L. M., Cabello\u2010Donayre, M., Vargas, P., Mart\u00ednez\u2010Garc\u00eda, M., S\u00e1nchez, C., Pineda\u2010Molina, E., Jim\u00e9nez, M., Molina, R., P\u00e9rez\u2010Victoria, J. M. Heme synthesis through the life cycle of the heme auxotrophic parasite\n                    <jats:italic>Leishmania major.<\/jats:italic>\n                    FASEB J. 33, 13367\u201313385 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201901274rr","type":"journal-article","created":{"date-parts":[[2019,9,25]],"date-time":"2019-09-25T17:49:00Z","timestamp":1569433740000},"page":"13367-13385","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Heme synthesis through the life cycle of the heme auxotrophic parasite\n                    <i>Leishmania major<\/i>"],"prefix":"10.1096","volume":"33","author":[{"given":"Lina M.","family":"Orrego","sequence":"first","affiliation":[{"name":"Instituto de Parasitolog\u00eda y Biomedicina L\u00f3pez\u2010Neyra, Consejo Superior de Investigaciones Cient\u00edficas (IPBLN\u2010CSIC), Parque Tecnol\u00f3gico de la Salud (PTS) Granada Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Cabello\u2010Donayre","sequence":"additional","affiliation":[{"name":"Instituto de Parasitolog\u00eda y Biomedicina L\u00f3pez\u2010Neyra, Consejo Superior de Investigaciones Cient\u00edficas (IPBLN\u2010CSIC), Parque Tecnol\u00f3gico de la Salud (PTS) Granada Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Vargas","sequence":"additional","affiliation":[{"name":"Instituto de Parasitolog\u00eda y Biomedicina L\u00f3pez\u2010Neyra, Consejo Superior de Investigaciones Cient\u00edficas (IPBLN\u2010CSIC), Parque Tecnol\u00f3gico de la Salud (PTS) Granada Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Mart\u00ednez\u2010Garc\u00eda","sequence":"additional","affiliation":[{"name":"Instituto de Parasitolog\u00eda y Biomedicina L\u00f3pez\u2010Neyra, Consejo Superior de Investigaciones Cient\u00edficas (IPBLN\u2010CSIC), Parque Tecnol\u00f3gico de la Salud (PTS) Granada Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Instituto de Parasitolog\u00eda y Biomedicina L\u00f3pez\u2010Neyra, Consejo Superior de Investigaciones Cient\u00edficas (IPBLN\u2010CSIC), Parque Tecnol\u00f3gico de la Salud (PTS) Granada Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estela","family":"Pineda\u2010Molina","sequence":"additional","affiliation":[{"name":"Instituto de Parasitolog\u00eda y Biomedicina L\u00f3pez\u2010Neyra, Consejo Superior de Investigaciones Cient\u00edficas (IPBLN\u2010CSIC), Parque Tecnol\u00f3gico de la Salud (PTS) Granada Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maribel","family":"Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Unidad de Entomolog\u00eda M\u00e9dica Servicio de Parasitolog\u00eda, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Molina","sequence":"additional","affiliation":[{"name":"Unidad de Entomolog\u00eda M\u00e9dica Servicio de Parasitolog\u00eda, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M.","family":"P\u00e9rez\u2010Victoria","sequence":"additional","affiliation":[{"name":"Instituto de Parasitolog\u00eda y Biomedicina L\u00f3pez\u2010Neyra, Consejo Superior de Investigaciones Cient\u00edficas (IPBLN\u2010CSIC), Parque Tecnol\u00f3gico de la Salud (PTS) Granada Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,9,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9629(15)40628-7"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0968-0004(89)90182-5"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2016.08.002"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2008.02.015"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003088"},{"key":"e_1_2_8_7_1","first-page":"703","article-title":"Remarques sur la nutrition des Trypanosomides et des bact\u00e9ries parah\u00e9motrophes le \u201cfer actif\u201d de baudisch","volume":"51","author":"Lwoff M.","year":"1933","journal-title":"Ann. 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