Integrative analysis of the heat shock response in Aspergillus fumigatus
Open accessAbstract
Background: Aspergillus fumigatus is a thermotolerant human-pathogenic mold and the most common cause of invasive aspergillosis (IA) in immunocompromised patients. Its predominance is based on several factors most of which are still unknown. The thermotolerance of A. fumigatus is one of the traits which have been assigned to pathogenicity. It allows the fungus to grow at temperatures up to and above that of a fevered human host. To elucidate the mechanisms of heat resistance, we analyzed the change of the A. fumigatus proteome during a temperature shift from 30°C to 48°C by 2D-fluorescence difference gel electrophoresis (DIGE). To improve 2D gel image analysis results, protein spot quantitation was optimized by missing value imputation and normalization. Differentially regulated proteins were compared to previously published transcriptome data of A. fumigatus . The study was augmented by bioinformatical analysis of transcription factor binding sites (TFBSs) in the promoter region of genes whose corresponding proteins were differentially regulated upon heat shock. Results: 91 differentially regulated protein spots, representing 64 different proteins, were identified by mass spectrometry (MS). They showed a continuous up-, down- or an oscillating regulation. Many of the identified proteins were involved in protein folding (chaperones), oxidative stress response, signal transduction, transcription, translation, carbohydrate and nitrogen metabolism. A correlation between alteration of transcript levels and corresponding proteins was detected for half of the differentially regulated proteins. Interestingly, some previously undescribed putative targets for the heat shock regulator Hsf1 were identified. This provides evidence for Hsf1-dependent regulation of mannitol biosynthesis, translation, cytoskeletal dynamics and cell division in A. fumigatus . Furthermore, computational analysis of promoters revealed putative binding sites for an AP-2alpha-like transcription factor upstream of some heat shock induced genes. Until now, this factor has only been found in vertebrates. Conclusions: Our newly established DIGE data analysis workflow yields improved data quality and is widely applicable for other DIGE datasets. Our findings suggest that the heat shock response in A. fumigatus differs from already well-studied yeasts and other filamentous fungi.
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Hsp90 levels increase following environmental challenges.
“Furthermore, although Hsp90 levels increase following environmental challenges, Hsp90 activity is tightly controlled via post-translational regulation and an autoregulatory loop involving the heat shock transcription factor, Hsf1.”
From Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs (2012) · cites this paper as [34]
Hsp90 is naturally abundant in fungal cells and is induced to even greater levels by heat shock and other proteotoxic stresses.
“Hsp90 is naturally abundant in fungal cells and is induced to even greater levels by heat shock and other proteotoxic stresses10,15,32-35.”
From Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs (2012) · cites this paper as [34]
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- Authors
- Albrecht, D., Guthke, R., Brakhage, A. A., & Kniemeyer, O.
- Affiliations
- Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE)
- Corresponding author
- Kniemeyer, Olaf
- Venue
- BMC Genomics
- Published
- 2010-01-15
- Volume
- 11
- Issue
- 1
- Pages
- 32-32
- ISSN
- 1471-2164 (ISSN-L)
- PMC
- PMC2820008
- OpenAlex
- W2079025500
- Cited by
- 105
- References
- 78
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 9 · 2020: 6 · 2019: 6 · 2018: 5 · 2017: 5 · 2016: 7 · 2015: 6 · 2014: 10 · 2013: 4 · 2012: 8
- FWCI
- 4.04
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Genomics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Keywords
- Aspergillus fumigatus, heat shock response, heat tolerance, proteome, differentially regulated proteins, HSF1, heat shock transcription factor, transcription factor binding sites, molecular chaperones, oxidative stress response, mannitol biosynthesis, invasive aspergillosis, missing data imputation
- MeSH terms
- Aspergillus fumigatus, Hot Temperature, Transcription Factors, Electrophoresis, Gel, Two-Dimensional, Gene Expression Regulation, Fungal, Heat-Shock Response, Computational Biology, Proteome, Gene Expression Profiling
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