{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:35:48Z","timestamp":1790908548376,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013993","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000}}],"reference-count":81,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Leishmania<\/jats:italic>\n                    spp. are intracellular parasites that cause leishmaniasis, a devastating disease with no effective treatment. These parasites are heme auxotrophs and must scavenge this essential cofactor from the host. Transcriptomic analysis of\n                    <jats:italic>Leishmania<\/jats:italic>\n                    <jats:italic>major<\/jats:italic>\n                    promastigotes cultured in the presence or absence of heme revealed numerous differentially expressed genes. Among those of unknown function,\n                    <jats:italic>LHR2<\/jats:italic>\n                    (\n                    <jats:italic>Leishmania<\/jats:italic>\n                    Heme Response-2) was the most upregulated gene in response to heme limitation.\n                    <jats:italic>LHR2<\/jats:italic>\n                    encodes a mitochondrial hemoprotein that likely protects this organelle from elevated levels of reactive oxygen species. It is essential during the promastigote stage, and loss of a single\n                    <jats:italic>LHR2<\/jats:italic>\n                    allele severely compromises intracellular replication and prevents the development of cutaneous leishmaniasis in mice. This essential function depends on LHR2\u2019s ability to bind heme. Complementation studies in\n                    <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                    revealed that LHR2 is an analogue of the yeast Dap1p, although it binds heme in a distinct manner. Importantly, LHR2 displays key structural differences from the most closely related human proteins. These findings highlight LHR2 as a critical factor in parasite survival and pathogenesis, and suggest it as a promising new target for antileishmanial drug development.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013993","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T18:45:22Z","timestamp":1772045122000},"page":"e1013993","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Heme limitation induces LHR2, an essential gene for Leishmania pathogenesis"],"prefix":"10.1371","volume":"22","author":[{"given":"Graciela","family":"Juez-Castillo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Garc\u00eda-Hern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Guerra-Arias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Vargas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Cabello-Donayre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan 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