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The Aspergillus pH-responsive transcription factor PacC regulates virulence
Elaine Bignell1, Susana Negrete-Urtasun, Ana Maria Calcagno
1Department of Infectious Diseases, Imperial College London, London W12 0NN, UK. e.bignell@imperial.ac.uk
Molecular Microbiology
|February 3, 2005
Summary
The Aspergillus nidulans PacC protein is crucial for fungal virulence in pulmonary aspergillosis. Disrupting its pH response pathway significantly reduces the pathogen
Area of Science:
- Medical Mycology
- Molecular Pathogenesis
- Host-Pathogen Interactions
Background:
- Pathogen adaptation to host environments is essential for disease initiation.
- Pulmonary aspergillosis is a serious opportunistic infection.
- The role of pH regulation in fungal virulence is increasingly recognized.
Purpose of the Study:
- To investigate the role of the Aspergillus nidulans PacC-mediated pH response in the pathogenesis of pulmonary aspergillosis.
- To determine how PacC influences fungal adaptation and virulence within the host.
Main Methods:
- Utilized mutational analysis in Aspergillus nidulans to study the PacC transcription factor.
- Infected neutropenic mice models to assess fungal virulence.
- Examined the impact of blocking pH signal transduction and PacC proteolytic processing.
Main Results:
- Elimination or disruption of PacC function significantly attenuated virulence in a murine model of pulmonary aspergillosis.
- Alkali-sensitive mutants exhibited limited fungal growth in vivo and reduced inflammatory cell infiltration.
- Constitutive activation of PacC led to increased mortality and extensive fungal invasive growth.
Conclusions:
- The Aspergillus nidulans PacC transcription factor plays a pivotal role in pulmonary pathogenesis.
- PacC-mediated pH response is essential for fungal adaptation and virulence.
- Targeting the PacC pathway could be a potential strategy for treating aspergillosis.