{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:49:13Z","timestamp":1790912953658,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010283","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T00:00:00Z","timestamp":1644796800000}}],"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T00:00:00Z","timestamp":1643760000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["210879364 C2"],"award-info":[{"award-number":["210879364 C2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["210879364 C5"],"award-info":[{"award-number":["210879364 C5"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008769","name":"University of W\u00fcrzburg","doi-asserted-by":"crossref","award":["Open Access Publication Fund"],"award-info":[{"award-number":["Open Access Publication Fund"]}],"id":[{"id":"10.13039\/501100008769","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Protein kinases play central roles in virtually all signaling pathways that enable organisms to adapt to their environment. Microbial pathogens must cope with severely restricted iron availability in mammalian hosts to invade and establish themselves within infected tissues. To uncover protein kinase signaling pathways that are involved in the adaptation of the pathogenic yeast\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    to iron limitation, we generated a comprehensive protein kinase deletion mutant library of a wild-type strain. Screening of this library revealed that the protein kinase Ire1, which has a conserved role in the response of eukaryotic cells to endoplasmic reticulum stress, is essential for growth of\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>albicans<\/jats:italic>\n                    under iron-limiting conditions. Ire1 was not necessary for the activity of the transcription factor Sef1, which regulates the response of the fungus to iron limitation, and Sef1 target genes that are induced by iron depletion were normally upregulated in\n                    <jats:italic>ire1<\/jats:italic>\n                    \u0394 mutants. Instead, Ire1 was required for proper localization of the high-affinity iron permease Ftr1 to the cell membrane. Intriguingly, iron limitation did not cause increased endoplasmic reticulum stress, and the transcription factor Hac1, which is activated by Ire1-mediated removal of the non-canonical intron in the\n                    <jats:italic>HAC1<\/jats:italic>\n                    mRNA, was dispensable for Ftr1 localization to the cell membrane and growth under iron-limiting conditions. Nevertheless, expression of a pre-spliced\n                    <jats:italic>HAC1<\/jats:italic>\n                    copy in\n                    <jats:italic>ire1<\/jats:italic>\n                    \u0394 mutants restored Ftr1 localization and rescued the growth defects of the mutants. Both\n                    <jats:italic>ire1<\/jats:italic>\n                    \u0394 and\n                    <jats:italic>hac1<\/jats:italic>\n                    \u0394 mutants were avirulent in a mouse model of systemic candidiasis, indicating that an appropriate response to endoplasmic reticulum stress is important for the virulence of\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>albicans<\/jats:italic>\n                    . However, the specific requirement of Ire1 for the functionality of the high-affinity iron permease Ftr1, a well-established virulence factor, even in the absence of endoplasmic reticulum stress uncovers a novel Hac1-independent essential role of Ire1 in iron acquisition and virulence of\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>albicans<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010283","type":"journal-article","created":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T13:42:32Z","timestamp":1643809352000},"page":"e1010283","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":33,"title":["The protein kinase Ire1 has a Hac1-independent essential role in iron uptake and virulence of Candida albicans"],"prefix":"10.1371","volume":"18","author":[{"given":"Bernardo","family":"Ram\u00edrez-Zavala","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Kr\u00fcger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Dunker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilse D.","family":"Jacobsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4227-8687","authenticated-orcid":true,"given":"Joachim","family":"Morschh\u00e4user","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,2,2]]},"reference":[{"key":"ppat.1010283.ref001","doi-asserted-by":"crossref","first-page":"100864","DOI":"10.1016\/j.mam.2020.100864","article-title":"Iron in infection and immunity","volume":"75","author":"M Nairz","year":"2020","journal-title":"Mol Aspects Med."},{"key":"ppat.1010283.ref002","doi-asserted-by":"crossref","first-page":"80","DOI":"10.3389\/fcimb.2013.00080","article-title":"Shared and distinct mechanisms of iron acquisition by bacterial and fungal pathogens of humans","volume":"3","author":"M Caza","year":"2013","journal-title":"Front Cell Infect 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