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Published on: March 18, 2012
The Peroxiredoxin Asp f3 Acts as Redox Sensor in Aspergillus fumigatus
Jana Marie Boysen1,2, Nauman Saeed1,2, Thomas Wolf3
1Junior Research Group Evolution of Microbial Interactions, Leibniz-Institute for Natural Product Research and Infection Biology-Hans Knöll Institute (HKI), Beutenbergstr. 11a, 07745 Jena, Germany.
Abstract:
The human pathogenic fungus Aspergillus fumigatus is readily eradicated by the innate immunity of immunocompetent human hosts, but can cause severe infections, such as invasive aspergillosis (IA), in immunocompromised individuals. During infection, the fungal redox homeostasis can be challenged by reactive oxygen species (ROS), either derived from the oxidative burst of innate immune cells or the action of antifungal drugs. The peroxiredoxin Asp f3 was found to be essential to cause IA in mice, but how Asp f3 integrates with fungal redox homeostasis remains unknown. Here, we show that in vivo, Asp f3 acts as a sensor for ROS. While global transcription in fungal hyphae under minimal growth conditions was fully independent of Asp f3, a robust induction of the oxidative stress response required the presence of the peroxiredoxin. Hyphae devoid of Asp f3 failed to activate several redox active genes, like members of the gliotoxin biosynthesis gene cluster and integral members of the Afyap1 regulon, the central activator of the ROS defense machinery in fungi. Upon deletion of the asp f3 gene Afyap1 displayed significantly reduced nuclear localization during ROS exposure, indicating that Asp f3 can act as an intracellular redox sensor for several target proteins.
Insights
The fungal protein Asp f3 is crucial for invasive aspergillosis (IA) by sensing reactive oxygen species (ROS). Without Asp f3, the fungus fails to activate key oxidative stress genes and its defense mechanisms.
Area of Science:
- Mycology
- Immunology
- Molecular Biology
Background:
- * *Aspergillus fumigatus* is a human pathogen causing invasive aspergillosis (IA) in immunocompromised individuals.
- * Fungal redox homeostasis is challenged by reactive oxygen species (ROS) during infection and antifungal treatment.
- * The peroxiredoxin Asp f3 is essential for IA, but its role in fungal redox homeostasis is unclear.
Purpose of the Study:
- * To investigate the function of Asp f3 in fungal redox homeostasis during infection.
- * To determine how Asp f3 integrates with the oxidative stress response in *Aspergillus fumigatus*.
Main Methods:
- * Gene deletion of *asp f3* in *Aspergillus fumigatus*.
- * Analysis of global gene transcription under oxidative stress conditions.
- * Investigation of nuclear localization of the transcription factor Afyap1.
Main Results:
- * Asp f3 is essential for the induction of the oxidative stress response in *Aspergillus fumigatus* hyphae.
- * Deletion of *asp f3* prevents the activation of redox-active genes, including gliotoxin biosynthesis and the Afyap1 regulon.
- * Asp f3 acts as an intracellular redox sensor, influencing the nuclear localization of Afyap1 during ROS exposure.
Conclusions:
- * Asp f3 plays a critical role in sensing ROS and activating fungal defense mechanisms against oxidative stress.
- * Asp f3 is a key component in the virulence of *Aspergillus fumigatus* by modulating its response to host immunity and antifungal drugs.
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