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dc.contributor.authorGrahl, Nora
dc.contributor.authorPuttikamonkul, Srisombat
dc.contributor.authorMacdonald, Jeffrey M.
dc.contributor.authorGamcsik, Michael P.
dc.contributor.authorNgo, Lisa Y.
dc.contributor.authorHohl, Tobias M.
dc.contributor.authorCramer, Robert A.
dc.date.accessioned2019-04-18T18:01:15Z
dc.date.available2019-04-18T18:01:15Z
dc.date.issued2011-07
dc.identifier.citationGrahl, Nora, Srisombat Puttikamonkul, Jeffrey M. Macdonald, Michael P. Gamcsik, Lisa Y. Ngo, Tobias M. Hohl, and Robert A. Cramer. “In Vivo Hypoxia and a Fungal Alcohol Dehydrogenase Influence the Pathogenesis of Invasive Pulmonary Aspergillosis.” PLoS Pathogens 7, no. 7 (July 21, 2011): e1002145. doi:10.1371/journal.ppat.1002145.en_US
dc.identifier.issn1553-7374
dc.identifier.urihttps://scholarworks.montana.edu/xmlui/handle/1/15447
dc.description.abstractCurrently, our knowledge of how pathogenic fungi grow in mammalian host environments is limited. Using a chemotherapeutic murine model of invasive pulmonary aspergillosis (IPA) and 1H-NMR metabolomics, we detected ethanol in the lungs of mice infected with Aspergillus fumigatus. This result suggests that A. fumigatus is exposed to oxygen depleted microenvironments during infection. To test this hypothesis, we utilized a chemical hypoxia detection agent, pimonidazole hydrochloride, in three immunologically distinct murine models of IPA (chemotherapeutic, X-CGD, and corticosteroid). In all three IPA murine models, hypoxia was observed during the course of infection. We next tested the hypothesis that production of ethanol in vivo by the fungus is involved in hypoxia adaptation and fungal pathogenesis. Ethanol deficient A. fumigatus strains showed no growth defects in hypoxia and were able to cause wild type levels of mortality in all 3 murine models. However, lung immunohistopathology and flow cytometry analyses revealed an increase in the inflammatory response in mice infected with an alcohol dehydrogenase null mutant strain that corresponded with a reduction in fungal burden. Consequently, in this study we present the first in vivo observations that hypoxic microenvironments occur during a pulmonary invasive fungal infection and observe that a fungal alcohol dehydrogenase influences fungal pathogenesis in the lung. Thus, environmental conditions encountered by invading pathogenic fungi may result in substantial fungal metabolism changes that influence subsequent host immune responses.en_US
dc.description.sponsorshipNational Institutes of Health COBRE grant RR020185; NIH/NIAID grant R01AI81838; M. J. Murdock Charitable Trust; Montana State University Agricultural Experiment Stationen_US
dc.language.isoenen_US
dc.rightsCC BY: This license lets you distribute, remix, tweak, and build upon this work, even commercially, as long as you credit the original creator for this work. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/legalcodeen_US
dc.titleIn vivo hypoxia and a fungal alcohol dehydrogenase influence the pathogenesis of invasive pulmonary aspergillosisen_US
dc.typeArticleen_US
mus.citation.issue7en_US
mus.citation.journaltitlePLoS Pathogensen_US
mus.citation.volume7en_US
mus.identifier.categoryLife Sciences & Earth Sciencesen_US
mus.identifier.doi10.1371/journal.ppat.1002145en_US
mus.relation.collegeCollege of Letters & Scienceen_US
mus.relation.departmentMicrobiology & Immunology.en_US
mus.relation.universityMontana State University - Bozemanen_US
mus.relation.researchgroupMT INBRE Bioinformatics and Biostatistics Core.en_US
mus.data.thumbpage4en_US
mus.contributor.orcidCramer, Robert A.|0000-0001-5503-5006en_US


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CC BY: This license lets you distribute, remix, tweak, and build upon this work, even commercially, as long as you credit the original creator for this work. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials.
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