{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:13:25Z","timestamp":1792174405511,"version":"4.4.0"},"reference-count":57,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2014,2,1]],"date-time":"2014-02-01T00:00:00Z","timestamp":1391212800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Iron acquisition is critical for the ability of the pathogenic yeast\n            <jats:named-content content-type=\"genus-species\">Cryptococcus neoformans<\/jats:named-content>\n            to cause disease in vertebrate hosts. In particular, iron overload exacerbates cryptococcal disease in an animal model, defects in iron acquisition attenuate virulence, and iron availability influences the expression of major virulence factors.\n            <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n            acquires iron by multiple mechanisms, including a ferroxidase-permease high-affinity system, siderophore uptake, and utilization of both heme and transferrin. In this study, we examined the expression of eight candidate ferric reductase genes and their contributions to iron acquisition as well as to ferric and cupric reductase activities. We found that loss of the\n            <jats:italic>FRE4<\/jats:italic>\n            gene resulted in a defect in production of the virulence factor melanin and increased susceptibility to azole antifungal drugs. In addition, the\n            <jats:italic>FRE2<\/jats:italic>\n            gene was important for growth on the iron sources heme and transferrin, which are relevant for proliferation in the host. Fre2 may participate with the ferroxidase Cfo1 of the high-affinity uptake system for growth on heme, because a mutant lacking both genes showed a more pronounced growth defect than the\n            <jats:italic>fre2<\/jats:italic>\n            single mutant. A role for Fre2 in iron acquisition is consistent with the attenuation of virulence observed for the\n            <jats:italic>fre2<\/jats:italic>\n            mutant. This mutant also was defective in accumulation in the brains of infected mice, a phenotype previously observed for mutants with defects in high-affinity iron uptake (e.g., the\n            <jats:italic>cfo1<\/jats:italic>\n            mutant). Overall, this study provides a more detailed view of the iron acquisition components required for\n            <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n            to cause cryptococcosis.\n          <\/jats:p>","DOI":"10.1128\/iai.01357-13","type":"journal-article","created":{"date-parts":[[2013,12,10]],"date-time":"2013-12-10T02:41:02Z","timestamp":1386643262000},"page":"839-850","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":88,"title":["Role of Ferric Reductases in Iron Acquisition and Virulence in the Fungal Pathogen Cryptococcus neoformans"],"prefix":"10.1128","volume":"82","author":[{"given":"Sanjay","family":"Saikia","sequence":"first","affiliation":[{"name":"Michael Smith Laboratories, Department of Microbiology and Immunology, and Faculty of Land and Food Systems, The University of British Columbia, Vancouver, British Columbia, 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