{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T09:02:10Z","timestamp":1790413330380,"version":"4.1.0"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T00:00:00Z","timestamp":1404172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2014,8,29]],"date-time":"2014-08-29T00:00:00Z","timestamp":1409270400000},"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":["mBio"],"published-print":{"date-parts":[[2014,8,29]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Infection with the dimorphic fungus<jats:named-content content-type=\"genus-species\">Histoplasma capsulatum<\/jats:named-content>results from the inhalation of contaminated soil. Disease outcome is variable and depends on the immune status of the host, number of organisms inhaled, and the<jats:named-content content-type=\"genus-species\">H. capsulatum<\/jats:named-content>strain.<jats:named-content content-type=\"genus-species\">H. capsulatum<\/jats:named-content>is divided into seven distinct clades based on phylogenetic analyses, and strains from two separate clades have been identified in North America (denoted as NAm strains). We characterized an<jats:named-content content-type=\"genus-species\">H. capsulatum<\/jats:named-content>isolate (WU24) from the NAm 1 lineage in relation to two other well-characterized<jats:italic>Histoplasma<\/jats:italic>isolates, the Panamanian strain G186A and the NAm 2 strain G217B. We determined that WU24 is a chemotype II strain and requires cell wall \u03b1-(1,3)-glucan for successful<jats:italic>in vitro<\/jats:italic>infection of macrophages. In a mouse model of histoplasmosis, WU24 exhibited a disease profile that was very similar to that of strain G186A at a high sublethal dose; however, at this dose G217B had markedly different kinetics. Surprisingly, infection with a lower dose mitigated many of the differences during the course of infection. The observed differences in fungal burden, disease kinetics, symptomology, and cytokine responses all indicate that there is a sophisticated relationship between host and fungus that drives the development and progression of histoplasmosis.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>Histoplasmosis has a wide range of clinical manifestations, presenting as mild respiratory distress, acute respiratory infection, or a life-threatening disseminated disease most often seen in immunocompromised patients. Additionally, the outcome appears to be dependent on the amount and strain of fungus inhaled. In this study, we characterized a recent clinical<jats:named-content content-type=\"genus-species\">H. capsulatum<\/jats:named-content>isolate that was collected from an HIV<jats:sup>+<\/jats:sup>individual in North America. In contrast to other isolates from the same lineage, this strain, WU24, infected both macrophages and wild-type mice. We determined that in contrast to many other North American strains, WU24 infection of macrophages is dependent on the presence of cell wall \u03b1-(1,3)-glucan. Surprisingly, comparison of WU24 with two previously characterized isolates revealed that many conclusions regarding relative strain virulence and certain hallmarks of histoplasmosis are dependent on the inoculum size.<\/jats:p>","DOI":"10.1128\/mbio.01376-14","type":"journal-article","created":{"date-parts":[[2014,7,2]],"date-time":"2014-07-02T10:14:46Z","timestamp":1404296086000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":48,"title":["Comparison of Phylogenetically Distinct<i>Histoplasma<\/i>Strains Reveals Evolutionarily Divergent Virulence Strategies"],"prefix":"10.1128","volume":"5","author":[{"given":"Victoria E.","family":"Sep\u00falveda","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA"},{"name":"Division of Biology and Biomedical Sciences, Washington University, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne L.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E.","family":"Goldman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"1","article-title":"An atlas of sensitivity to tuberculin, PPD-B, and histoplasmin in the United States","volume":"99","author":"Edwards LB","year":"1969","unstructured":"EdwardsLB AcquavivaFA LivesayVT CrossFW PalmerCE . 1969. 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