{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:28:18Z","timestamp":1791520098153,"version":"4.3.4"},"reference-count":56,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2018,1,2]],"date-time":"2018-01-02T00:00:00Z","timestamp":1514851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,3,7]],"date-time":"2018-03-07T00:00:00Z","timestamp":1520380800000},"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":["R21-AI117122"],"award-info":[{"award-number":["R21-AI117122"]}],"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"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01-AI035681"],"award-info":[{"award-number":["R01-AI035681"]}],"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":["R01-AI093553"],"award-info":[{"award-number":["R01-AI093553"]}],"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":["R01-AI059639"],"award-info":[{"award-number":["R01-AI059639"]}],"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":[[2018,3,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The ability to grow at mammalian body temperatures is critical for pathogen infection of humans. For the thermally dimorphic fungal pathogen\n            <jats:italic>Histoplasma capsulatum<\/jats:italic>\n            , elevated temperature is required for differentiation of mycelia or conidia into yeast cells, a step critical for invasion and replication within phagocytic immune cells. Posttranslational glycosylation of extracellular proteins characterizes factors produced by the pathogenic yeast cells but not those of avirulent mycelia, correlating glycosylation with infection.\n            <jats:italic>Histoplasma<\/jats:italic>\n            yeast cells lacking the Pmt1 and Pmt2 protein mannosyltransferases, which catalyze O-linked mannosylation of proteins, are severely attenuated during infection of mammalian hosts. Cells lacking Pmt2 have altered surface characteristics that increase recognition of yeast cells by the macrophage mannose receptor and reduce recognition by the \u03b2-glucan receptor Dectin-1. Despite these changes, yeast cells lacking these factors still associate with and survive within phagocytes. Depletion of macrophages or neutrophils\n            <jats:italic>in vivo<\/jats:italic>\n            does not recover the virulence of the mutant yeast cells. We show that yeast cells lacking Pmt functions are more sensitive to thermal stress\n            <jats:italic>in vitro<\/jats:italic>\n            and consequently are unable to productively infect mice, even in the absence of fever. Treatment of mice with cyclophosphamide reduces the normal core body temperature of mice, and this decrease is sufficient to restore the infectivity of O-mannosylation-deficient yeast cells. These findings demonstrate that O-mannosylation of proteins increases the thermotolerance of\n            <jats:italic>Histoplasma<\/jats:italic>\n            yeast cells, which facilitates infection of mammalian hosts.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            For dimorphic fungal pathogens, mammalian body temperature can have contrasting roles. Mammalian body temperature induces differentiation of the fungal pathogen\n            <jats:italic>Histoplasma capsulatum<\/jats:italic>\n            into a pathogenic state characterized by infection of host phagocytes. On the other hand, elevated temperatures represent a significant barrier to infection by many microbes. By functionally characterizing cells lacking O-linked mannosylation enzymes, we show that protein mannosylation confers thermotolerance on\n            <jats:italic>H.\u00a0capsulatum<\/jats:italic>\n            , enabling infection of mammalian hosts.\n          <\/jats:p>","DOI":"10.1128\/mbio.02121-17","type":"journal-article","created":{"date-parts":[[2018,1,8]],"date-time":"2018-01-08T10:36:47Z","timestamp":1515407807000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["O-Mannosylation of Proteins Enables\n            <i>Histoplasma<\/i>\n            Yeast Survival at Mammalian Body Temperatures"],"prefix":"10.1128","volume":"9","author":[{"given":"Andrew L.","family":"Garfoot","sequence":"first","affiliation":[{"name":"Department of Microbiology, Ohio State University, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristie D.","family":"Goughenour","sequence":"additional","affiliation":[{"name":"Department of Microbiology, 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, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murugesan V. S.","family":"Rajaram","sequence":"additional","affiliation":[{"name":"Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Ohio State University, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry S.","family":"Schlesinger","sequence":"additional","affiliation":[{"name":"Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Ohio State University, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce S.","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin, Madison, Wisconsin, USA"},{"name":"Departments of Medicine and Medical Microbiology and Immunology, University of Wisconsin, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad A.","family":"Rappleye","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Ohio State University, Columbus, Ohio, USA"},{"name":"Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Ohio State University, Columbus, Ohio, 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