{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T06:06:53Z","timestamp":1785564413692,"version":"3.56.0"},"reference-count":36,"publisher":"Rockefeller University Press","issue":"8","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,4,19]]},"abstract":"<jats:p>Systemic fungal infections are becoming more common and difficult to treat, yet the pathogenesis of these infectious diseases remains poorly understood. In many cases, pathogenicity can be attributed to the ability of the fungi to adhere to target tissues, but the lack of tractable genetic systems has limited progress in understanding and interfering with the offending fungal products. In Blastomyces dermatitidis, the agent of blastomycosis, a respiratory and disseminated mycosis of people and animals worldwide, expression of the putative adhesin encoded by the WI-1 gene was investigated as a possible virulence factor. DNA-mediated gene transfer was used to disrupt the WI-1 locus by allelic replacement, resulting in impaired binding and entry of yeasts into macrophages, loss of adherence to lung tissue, and abolishment of virulence in mice; each of these properties was fully restored after reconstitution of WI-1 by means of gene transfer. These findings establish the pivotal role of WI-1 in adherence and virulence of B. dermatitidis yeasts. To our knowledge, they offer the first example of a genetically proven virulence determinant among systemic dimorphic fungi, and underscore the value of reverse genetics for studies of pathogenesis in these organisms.<\/jats:p>","DOI":"10.1084\/jem.189.8.1207","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"1207-1216","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":132,"title":["Targeted Gene Disruption Reveals an Adhesin Indispensable for Pathogenicity of <i>Blastomyces dermatitidis <\/i>"],"prefix":"10.1084","volume":"189","author":[{"given":"T.","family":"Tristan Brandhorst","sequence":"first","affiliation":[{"name":"From the *Department of Pediatrics, the \u2021Department of Internal Medicine, the \u00a7Department of Medical Microbiology and Immunology, and \u2009the \u2016Department of Pathology and Laboratory Medicine, and the \u00b6Comprehensive Cancer Center, University of \u2009Wisconsin Medical School, Madison, Wisconsin 53792"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"W\u00fcthrich","sequence":"additional","affiliation":[{"name":"From the *Department of Pediatrics, the \u2021Department of Internal Medicine, the \u00a7Department of Medical Microbiology and Immunology, and \u2009the \u2016Department of Pathology and Laboratory Medicine, and the \u00b6Comprehensive Cancer Center, University of \u2009Wisconsin Medical School, Madison, Wisconsin 53792"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Warner","sequence":"additional","affiliation":[{"name":"From the *Department of Pediatrics, the \u2021Department of Internal Medicine, the \u00a7Department of Medical Microbiology and Immunology, and \u2009the \u2016Department of Pathology and Laboratory Medicine, and the \u00b6Comprehensive Cancer Center, University of \u2009Wisconsin Medical School, Madison, Wisconsin 53792"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Klein","sequence":"additional","affiliation":[{"name":"From the *Department of Pediatrics, the \u2021Department of Internal Medicine, the \u00a7Department of Medical Microbiology and Immunology, and \u2009the \u2016Department of Pathology and Laboratory Medicine, and the \u00b6Comprehensive Cancer Center, University of \u2009Wisconsin Medical School, Madison, Wisconsin 53792"},{"name":"From the *Department of Pediatrics, the \u2021Department of Internal Medicine, the \u00a7Department of Medical Microbiology and Immunology, and \u2009the \u2016Department of Pathology and Laboratory Medicine, and the \u00b6Comprehensive Cancer Center, University of \u2009Wisconsin Medical School, Madison, Wisconsin 53792"},{"name":"From the *Department of Pediatrics, the \u2021Department of Internal Medicine, the \u00a7Department of Medical Microbiology and Immunology, and \u2009the \u2016Department of Pathology and Laboratory Medicine, and the \u00b6Comprehensive Cancer Center, University of \u2009Wisconsin Medical School, Madison, Wisconsin 53792"},{"name":"From the *Department of Pediatrics, the \u2021Department of Internal Medicine, the \u00a7Department of Medical Microbiology and Immunology, and \u2009the \u2016Department of Pathology and Laboratory Medicine, and the \u00b6Comprehensive Cancer Center, University of \u2009Wisconsin Medical School, Madison, Wisconsin 53792"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1999,4,19]]},"reference":[{"key":"2023072508390701100_B1","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1126\/science.7702654","article-title":"The emerging fungal threat","volume":"266","author":"Sternberg","year":"1994","journal-title":"Science"},{"key":"2023072508390701100_B2"},{"key":"2023072508390701100_B3","first-page":"2777","article-title":"Isolation of telomerelike 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