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Histological Quantification to Determine Lung Fungal Burden in Experimental Aspergillosis
Published on: March 9, 2018
Cytotoxic substances from Aspergillus fumigatus in oxygenated or poorly oxygenated environment
Akira Watanabe1, Katsuhiko Kamei, Toshikazu Sekine
1Research Center for Pathogenic Fungi and Microbial Toxicoses, Chiba University, Chiba City, Japan. fewata@restaff.chiba-u.jp
Abstract:
Aspergillus fumigatus often causes serious health problems. The airway of the human body, the most common initial site of damage, is always exposed to an oxygenated condition, and the oxygen concentration may play a critical role in the virulence of A. fumigatus. In this study, oxygen content, fungal growth, the production of cytotoxic substance(s) in the fungal culture, and their relationship were investigated. Two clinical strains of A. fumigatus were cultured under certain oxygen contents (10, 14 and 20%), and cytotoxicity of their culture filtrates on murine macrophages and their fungal growth were evaluated. The components of these filtrates were analyzed by gas chromatography-mass spectrometry. All culture filtrates contained gliotoxin and showed potent cytotoxicity on macrophages at very low concentration. The amount of gliotoxin in the culture filtrate prepared at 10% oxygen was markedly less, but diminutions in fungal growth and cytotoxicity of this culture filtrate were negligible. These results suggest that a well-oxygenated condition is suitable for the production of gliotoxin by A. fumigatus. A significant role of cytotoxic substances(s) other than gliotoxin is also suggested.
Insights
Oxygen levels impact Aspergillus fumigatus virulence. Higher oxygen (20%) boosts gliotoxin production, a key cytotoxic substance, though other factors also contribute to fungal damage.
Area of Science:
- Medical Mycology
- Environmental Microbiology
- Pathogen Virulence Factors
Background:
- Aspergillus fumigatus is an opportunistic fungal pathogen causing significant human health issues.
- The respiratory tract, a common infection site, is exposed to varying oxygen concentrations.
- Oxygen levels are hypothesized to influence A. fumigatus virulence and toxin production.
Purpose of the Study:
- To investigate the effect of different oxygen concentrations on A. fumigatus growth.
- To assess the impact of oxygen on the production of cytotoxic substances, including gliotoxin.
- To explore the relationship between oxygen, fungal growth, and cytotoxicity.
Main Methods:
- Two clinical A. fumigatus strains were cultured at 10%, 14%, and 20% oxygen.
- Culture filtrates were tested for cytotoxicity against murine macrophages.
- Fungal growth was quantified.
- Filtrate components were analyzed using gas chromatography-mass spectrometry.
Main Results:
- All culture filtrates contained gliotoxin and exhibited potent macrophage cytotoxicity.
- Gliotoxin production was significantly lower at 10% oxygen compared to higher concentrations.
- Despite reduced gliotoxin at 10% oxygen, fungal growth and overall filtrate cytotoxicity showed negligible decrease.
- Gas chromatography-mass spectrometry identified gliotoxin and suggested the presence of other cytotoxic substances.
Conclusions:
- Well-oxygenated conditions (e.g., 20% oxygen) favor gliotoxin production in A. fumigatus.
- Cytotoxic substances other than gliotoxin likely play a significant role in A. fumigatus-mediated damage.
- Oxygen tension is a critical environmental factor modulating A. fumigatus virulence.
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