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dc.contributor.authorBarker, Bridget M.
dc.contributor.authorKroll, Kristin
dc.contributor.authorVödisch, Martin
dc.contributor.authorMazurie, Aurélien J.
dc.contributor.authorKniemeyer, Olaf
dc.contributor.authorCramer, Robert A.
dc.date.accessioned2019-04-22T19:33:45Z
dc.date.available2019-04-22T19:33:45Z
dc.date.issued2012-02
dc.identifier.citationBarker, Bridget M., Kristin Kroll, Martin Vödisch, Aurélien J. Mazurie, Olaf Kniemeyer, and Robert A. Cramer. “Transcriptomic and Proteomic Analyses of the Aspergillus Fumigatus Hypoxia Response Using an Oxygen-Controlled Fermenter.” BMC Genomics 13, no. 1 (2012): 62. doi:10.1186/1471-2164-13-62.en_US
dc.identifier.issn1471-2164
dc.identifier.urihttps://scholarworks.montana.edu/xmlui/handle/1/15454
dc.description.abstractBackground Aspergillus fumigatus is a mold responsible for the majority of cases of aspergillosis in humans. To survive in the human body, A. fumigatus must adapt to microenvironments that are often characterized by low nutrient and oxygen availability. Recent research suggests that the ability of A. fumigatus and other pathogenic fungi to adapt to hypoxia contributes to their virulence. However, molecular mechanisms of A. fumigatus hypoxia adaptation are poorly understood. Thus, to better understand how A. fumigatus adapts to hypoxic microenvironments found in vivo during human fungal pathogenesis, the dynamic changes of the fungal transcriptome and proteome in hypoxia were investigated over a period of 24 hours utilizing an oxygen-controlled fermenter system. Results Significant increases in transcripts associated with iron and sterol metabolism, the cell wall, the GABA shunt, and transcriptional regulators were observed in response to hypoxia. A concomitant reduction in transcripts was observed with ribosome and terpenoid backbone biosynthesis, TCA cycle, amino acid metabolism and RNA degradation. Analysis of changes in transcription factor mRNA abundance shows that hypoxia induces significant positive and negative changes that may be important for regulating the hypoxia response in this pathogenic mold. Growth in hypoxia resulted in changes in the protein levels of several glycolytic enzymes, but these changes were not always reflected by the corresponding transcriptional profiling data. However, a good correlation overall (R2 = 0.2, p < 0.05) existed between the transcriptomic and proteomics datasets for all time points. The lack of correlation between some transcript levels and their subsequent protein levels suggests another regulatory layer of the hypoxia response in A. fumigatus. Conclusions Taken together, our data suggest a robust cellular response that is likely regulated both at the transcriptional and post-transcriptional level in response to hypoxia by the human pathogenic mold A. fumigatus. As with other pathogenic fungi, the induction of glycolysis and transcriptional down-regulation of the TCA cycle and oxidative phosphorylation appear to major components of the hypoxia response in this pathogenic mold. In addition, a significant induction of the transcripts involved in ergosterol biosynthesis is consistent with previous observations in the pathogenic yeasts Candida albicans and Cryptococcus neoformans indicating conservation of this response to hypoxia in pathogenic fungi. Because ergosterol biosynthesis enzymes also require iron as a co-factor, the increase in iron uptake transcripts is consistent with an increased need for iron under hypoxia. However, unlike C. albicans and C. neoformans, the GABA shunt appears to play an important role in reducing NADH levels in response to hypoxia in A. fumigatus and it will be intriguing to determine whether this is critical for fungal virulence. Overall, regulatory mechanisms of the A. fumigatus hypoxia response appear to involve both transcriptional and post-transcriptional control of transcript and protein levels and thus provide candidate genes for future analysis of their role in hypoxia adaptation and fungal virulence.en_US
dc.description.sponsorshipNational Institute of Health grant RR020185; NIH/NIAID grant R01AI81838; Montana State University Agricultural Experiment Station; Hans-Knoell-Institute; German-Israeli Foundation for Scientific Research and Development Grant No. 996-47.12/2008; International Leibniz Research School for Microbial and Biomolecular Interactionsen_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.titleTranscriptomic and proteomic analyses of the Aspergillus fumigatus hypoxia response using an oxygen-controlled fermenteren_US
dc.typeArticleen_US
mus.citation.issue62en_US
mus.citation.journaltitleBMC Genomicsen_US
mus.citation.volume13en_US
mus.identifier.categoryLife Sciences & Earth Sciencesen_US
mus.identifier.doi10.1186/1471-2164-13-62en_US
mus.relation.collegeCollege of Letters & Scienceen_US
mus.relation.collegeOther Departments & Programsen_US
mus.relation.departmentIT Center.en_US
mus.relation.departmentMicrobiology & Immunology.en_US
mus.relation.universityMontana State University - Bozemanen_US
mus.relation.researchgroupIT Center.en_US
mus.relation.researchgroupMT INBRE Bioinformatics and Biostatistics Core.en_US
mus.data.thumbpage6en_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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