dc.contributor.author | Steenwyk, Jacob L. | |
dc.date.accessioned | 2020-04-06T16:52:36Z | |
dc.date.available | 2020-04-06T16:52:36Z | |
dc.date.issued | 2019-04-24 | |
dc.identifier.citation | Ries LNA, Steenwyk JL, de Castro PA, de Lima PBA, Almeida F, de Assis LJ, Manfiolli AO, Takahashi-Nakaguchi A, Kusuya Y, Hagiwara D, Takahashi H, Wang X, Obar JJ, Rokas A and Goldman GH (2019) Nutritional Heterogeneity Among Aspergillus fumigatus Strains Has Consequences for Virulence in a Strain- and Host-Dependent Manner. Front. Microbiol. 10:854. doi: 10.3389/fmicb.2019.00854 | en_US |
dc.identifier.issn | 1664-302X | |
dc.identifier.uri | https://ir.vanderbilt.edu/xmlui/handle/1803/9888 | |
dc.description | Only Vanderbilt University affiliated authors are listed on VUIR. For a full list of authors, access the version of record at https://www.frontiersin.org/articles/10.3389/fmicb.2019.00854/full | |
dc.description.abstract | Acquisition and subsequent metabolism of different carbon and nitrogen sources have been shown to play an important role in virulence attributes of the fungal pathogen Aspergillus fumigatus, such as the secretion of host tissue-damaging proteases and fungal cell wall integrity. We examined the relationship between the metabolic processes of carbon catabolite repression (CCR), nitrogen catabolite repression (NCR) and virulence in a variety of A. fumigatus clinical isolates. A considerable amount of heterogeneity with respect to the degree of CCR and NCR was observed and a positive correlation between NCR and virulence in a neutropenic mouse model of pulmonary aspergillosis (PA) was found. Isolate Afs35 was selected for further analysis and compared to the reference strain A1163, with both strains presenting the same degree of virulence in a neutropenic mouse model of PA. Afs35 metabolome analysis in physiological-relevant carbon sources indicated an accumulation of intracellular sugars that also serve as cell wall polysaccharide precursors. Genome analysis showed an accumulation of missense substitutions in the regulator of protease secretion and in genes encoding enzymes required for cell wall sugar metabolism. Based on these results, the virulence of strains Afs35 and A1163 was assessed in a triamcinolone murine model of PA and found to be significantly different, confirming the known importance of using different mouse models to assess strain-specific pathogenicity. These results highlight the importance of nitrogen metabolism for virulence and provide a detailed example of the heterogeneity that exists between A. fumigatus isolates with consequences for virulence in a strain-specific and host-dependent manner. | en_US |
dc.description.sponsorship | JO was supported in part by institutional startup funds and in part through the Dartmouth Lung Biology Center for Molecular, Cellular, and Translational Research grant P30 GM106394 (PI: Bruce A. Stanton) and Center for Molecular, Cellular, and Translational Immunological Research grant P30 GM103415 (PI: William R. Green). FA was supported by a FAPESP young researcher fellowship (2016/03322-7). LR was supported by a FAPESP young researcher fellowship (2017/14159-2). JS was supported by the Graduate Program in Biological Sciences at Vanderbilt University and AR was supported, in part, by the National Science Foundation (DEB-1442113), the Vanderbilt Discovery Grant Program, the Burroughs Wellcome Fund, and the Guggenheim Foundation. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | FRONTIERS IN MICROBIOLOGY | en_US |
dc.rights | Copyright © 2019 Ries, Steenwyk, de Castro, de Lima, Almeida, de Assis, Manfiolli, Takahashi-Nakaguchi, Kusuya, Hagiwara, Takahashi, Wang, Obar, Rokas and Goldman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. | |
dc.rights | This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. | |
dc.source.uri | https://www.frontiersin.org/articles/10.3389/fmicb.2019.00854/full | |
dc.source.uri | https://www.frontiersin.org/articles/10.3389/fmicb.2019.00854/full | |
dc.subject | Aspergillus fumigatus | en_US |
dc.subject | clinical isolates | en_US |
dc.subject | carbon and nitrogen catabolite repression | en_US |
dc.subject | genome comparison | en_US |
dc.subject | cell wall; | en_US |
dc.subject | virulence | en_US |
dc.title | Nutritional Heterogeneity Among Aspergillus fumigatus Strains Has Consequences for Virulence in a Strain- and Host-Dependent Manner | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.3389/fmicb.2019.00854 | |
dc.identifier.doi | 10.3389/fmicb.2019.00854 | |