{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:44:53Z","timestamp":1790037893509,"version":"4.0.1"},"reference-count":31,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T00:00:00Z","timestamp":1104537600000},"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":["Eukaryot Cell"],"published-print":{"date-parts":[[2005,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Laccases are thought to be important to the virulence of many fungal pathogens by producing melanin, a presumed oxygen radical scavenger. A laccase in\n            <jats:italic>Cryptococcus neoformans<\/jats:italic>\n            has been shown to synthesize melanin and contributes to the virulence and the survival in macrophages of this fungal pathogen. One\n            <jats:italic>C. neoformans<\/jats:italic>\n            laccase gene,\n            <jats:italic>LAC1<\/jats:italic>\n            , previously called\n            <jats:italic>CNLAC1<\/jats:italic>\n            , has been extensively studied, and we describe a homologous gene,\n            <jats:italic>LAC2<\/jats:italic>\n            , that is found 8 kb away from\n            <jats:italic>LAC1<\/jats:italic>\n            in the genome. In this study we report a role for both laccases, in addition to the thiol peroxidase, Tsa1, in oxidative and nitrosative stress resistance mechanisms of\n            <jats:italic>C. neoformans<\/jats:italic>\n            . With use of real-time PCR, similar changes in expression of the two laccase genes occur in response to oxidative and nitrosative stresses, but only the regulation of the\n            <jats:italic>LAC2<\/jats:italic>\n            gene during stress is influenced by Tsa1. Both laccases contribute to melanin production using L-dopa as a substrate and are differentially localized in the cell based on green fluorescent protein fusions. A single deletion of either\n            <jats:italic>LAC1<\/jats:italic>\n            or\n            <jats:italic>LAC2<\/jats:italic>\n            alone had no effect on sensitivity to H\n            <jats:sub>2<\/jats:sub>\n            O\n            <jats:sub>2<\/jats:sub>\n            or nitric oxide. However, deletion of either\n            <jats:italic>LAC1<\/jats:italic>\n            or\n            <jats:italic>LAC2<\/jats:italic>\n            in combination with a\n            <jats:italic>TSA1<\/jats:italic>\n            deletion resulted in a slight peroxide sensitivity, and a\n            <jats:italic>lac2<\/jats:italic>\n            \u0394\n            <jats:italic>tsa1<\/jats:italic>\n            \u0394 deletion strain was sensitive to nitric oxide stress. In addition, the deletion of both laccases reduces survival of\n            <jats:italic>C. neoformans<\/jats:italic>\n            in primary macrophages. Based on our expression and functional analysis, we propose a novel model for the interaction of these two systems, which are both important for virulence.\n          <\/jats:p>","DOI":"10.1128\/ec.4.1.202-208.2005","type":"journal-article","created":{"date-parts":[[2005,1,11]],"date-time":"2005-01-11T01:16:15Z","timestamp":1105406175000},"page":"202-208","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":113,"title":["Distinct Stress Responses of Two Functional Laccases in\n            <i>Cryptococcus neoformans<\/i>\n            Are Revealed in the Absence of the Thiol-Specific Antioxidant Tsa1"],"prefix":"10.1128","volume":"4","author":[{"given":"Tricia A.","family":"Missall","sequence":"first","affiliation":[{"name":"Edward A. Doisy Department of Biochemistry and Molecular Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason M.","family":"Moran","sequence":"additional","affiliation":[{"name":"Edward A. Doisy Department of Biochemistry and Molecular Biology"},{"name":"Department of Molecular Microbiology and Immunology, St. Louis University School of Medicine, St. Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Corbett","sequence":"additional","affiliation":[{"name":"Edward A. Doisy Department of Biochemistry and Molecular Biology"},{"name":"Department of Molecular Microbiology and Immunology, St. Louis University School of Medicine, St. Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer K.","family":"Lodge","sequence":"additional","affiliation":[{"name":"Edward A. Doisy Department of Biochemistry and Molecular Biology"},{"name":"Department of Molecular Microbiology and Immunology, St. Louis University School of Medicine, St. Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.56.5.1371-1375.1988"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.3.1538-1547.2003"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-148-8-2607"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2003.10.029"},{"key":"e_1_3_2_6_2","first-page":"538","volume":"14","year":"1993","unstructured":"Fujimura, H., and Y. Sakuma. 1993. Simplified isolation of chromosomal and plasmid DNA from yeasts. 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