{"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":1790413330365,"version":"4.1.0"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2016,4,19]],"date-time":"2016-04-19T00:00:00Z","timestamp":1461024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2016,5,4]],"date-time":"2016-05-04T00:00:00Z","timestamp":1462320000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01-AI083335"],"award-info":[{"award-number":["R01-AI083335"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32-AI112542"],"award-info":[{"award-number":["T32-AI112542"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2016,5,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n The fungal pathogen\n Histoplasma capsulatum<\/jats:named-content>\n parasitizes host phagocytes. To avoid antimicrobial immune responses,\n Histoplasma<\/jats:italic>\n yeasts must minimize their detection by host receptors while simultaneously interacting with the phagocyte. Pathogenic\n Histoplasma<\/jats:italic>\n yeast cells, but not avirulent mycelial cells, secrete the Eng1 protein, which is a member of the glycosylhydrolase 81 (GH81) family. We show that\n Histoplasma<\/jats:italic>\n Eng1 is a glucanase that hydrolyzes \u03b2-(1,3)-glycosyl linkages but is not required for\n Histoplasma<\/jats:italic>\n growth\n in vitro<\/jats:italic>\n or for cell separation. However,\n Histoplasma<\/jats:italic>\n yeasts lacking Eng1 function have attenuated virulence\n in vivo<\/jats:italic>\n , particularly during the cell-mediated immunity stage.\n Histoplasma<\/jats:italic>\n yeasts deficient for Eng1 show increased exposure of cell wall \u03b2-glucans, which results in enhanced binding to the Dectin-1 \u03b2-glucan receptor. Consistent with this, Eng1-deficient yeasts trigger increased tumor necrosis factor alpha (TNF-\u03b1) and interleukin-6 (IL-6) cytokine production from macrophages and dendritic cells. While not responsible for large-scale cell wall structure and function, the secreted Eng1 reduces levels of exposed \u03b2-glucans at the yeast cell wall, thereby diminishing potential recognition by Dectin-1 and proinflammatory cytokine production by phagocytes. In \u03b1-glucan-producing\n Histoplasma<\/jats:italic>\n strains, Eng1 acts in concert with \u03b1-glucan to minimize \u03b2-glucan exposure: \u03b1-glucan provides a masking function by covering the \u03b2-glucan-rich cell wall, while Eng1 removes any remaining exposed \u03b2-glucans. Thus,\n Histoplasma<\/jats:italic>\n Eng1 has evolved a specialized pathogenesis function to remove exposed \u03b2-glucans, thereby enhancing the ability of yeasts to escape detection by host phagocytes.\n <\/jats:p>\n \n IMPORTANCE<\/jats:bold>\n The success of\n Histoplasma capsulatum<\/jats:named-content>\n as an intracellular pathogen results, in part, from an ability to minimize its detection by receptors on phagocytic cells of the immune system. In this study, we showed that\n Histoplasma<\/jats:italic>\n pathogenic yeast cells, but not avirulent mycelia, secrete a \u03b2-glucanase, Eng1, which reduces recognition of fungal cell wall \u03b2-glucans. We demonstrated that the Eng1 \u03b2-glucanase promotes\n Histoplasma<\/jats:italic>\n virulence by reducing levels of surface-exposed \u03b2-glucans on yeast cells, thereby enabling\n Histoplasma<\/jats:italic>\n yeasts to escape detection by the host \u03b2-glucan receptor, Dectin-1. As a consequence, phagocyte recognition of\n Histoplasma<\/jats:italic>\n yeasts is reduced, leading to less proinflammatory cytokine production by phagocytes and less control of\n Histoplasma<\/jats:italic>\n infection\n in vivo<\/jats:italic>\n . Thus,\n Histoplasma<\/jats:italic>\n yeasts express two mechanisms to avoid phagocyte detection: masking of cell wall \u03b2-glucans by \u03b1-glucan and enzymatic removal of exposed \u03b2-glucans by the Eng1 \u03b2-glucanase.\n <\/jats:p>","DOI":"10.1128\/mbio.01388-15","type":"journal-article","created":{"date-parts":[[2016,4,19]],"date-time":"2016-04-19T21:13:21Z","timestamp":1461100401000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":97,"title":["The Eng1 \u03b2-Glucanase Enhances\n Histoplasma<\/i>\n Virulence by Reducing \u03b2-Glucan Exposure"],"prefix":"10.1128","volume":"7","author":[{"given":"Andrew L.","family":"Garfoot","sequence":"first","affiliation":[{"name":"Departments of Microbiology and Microbial Infection and Immunity, Ohio State University, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Shen","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Microbial Infection and Immunity, Ohio State University, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"W\u00fcthrich","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin\u2014Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce S.","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin\u2014Madison, Madison, Wisconsin, USA"},{"name":"Departments of Medicine and Medical Microbiology and Immunology, University of Wisconsin\u2014Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad A.","family":"Rappleye","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Microbial Infection and Immunity, Ohio State University, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/febs.13389"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.4049\/jimmunol.132.5.2593","article-title":"Inhibition of growth of Histoplasma capsulatum by lymphokine-stimulated macrophages","volume":"132","author":"Wu-Hsieh B","year":"1984","unstructured":"Wu-Hsieh B, Howard DH. 1984. Inhibition of growth of Histoplasma capsulatum by lymphokine-stimulated macrophages. 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