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A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
Published on: February 19, 2019
A regulator of Aspergillus fumigatus extracellular proteolytic activity is dispensable for virulence
Anna Bergmann1, Thomas Hartmann, Timothy Cairns
1Research Center for Infectious Diseases, Julius-Maximilians-University, Würzburg, Germany.
Abstract:
Virulence of the fungal pathogen Aspergillus fumigatus is in part based on the saprophytic lifestyle that this mold has evolved. A crucial function for saprophytism resides in secreted proteases that allow assimilation of proteinaceous substrates. The impact of extracellular proteolytic activities on the pathogenesis of aspergillosis, however, remains controversial. In order to address this issue, characterization of a conserved regulatory factor, PrtT, that acts on expression of secreted proteases was pursued. Expression of PrtT appears to be regulated posttranscriptionally, and the existence of an mRNA leader sequence implies translational control via eIF2alpha kinase signaling. Phenotypic classification of a prtTDelta deletion mutant revealed that expression of several major extracellular proteases is PrtT dependent, resulting in the inability to utilize protein as a nutritional source. Certain genes encoding secreted proteases are not regulated by PrtT. Most strikingly, the deletant strain is not attenuated in virulence when tested in a leukopenic mouse model, which makes a strong case for reconsidering any impact of secreted proteases in pulmonary aspergillosis.
Insights
The regulatory factor PrtT controls secreted proteases in Aspergillus fumigatus, impacting its ability to use protein as a nutrient. However, PrtT deletion did not affect virulence in a mouse model of aspergillosis.
Area of Science:
- Medical Mycology
- Molecular Biology
- Pathogenesis Research
Background:
- Aspergillus fumigatus virulence is linked to its saprophytic lifestyle, utilizing secreted proteases for nutrient assimilation.
- The role of extracellular proteolytic activity in aspergillosis pathogenesis remains debated.
- Understanding regulatory mechanisms of secreted proteases is crucial for fungal virulence studies.
Purpose of the Study:
- To characterize the regulatory factor PrtT, which controls the expression of secreted proteases in Aspergillus fumigatus.
- To investigate the impact of PrtT on fungal nutrition and virulence.
- To clarify the contribution of secreted proteases to aspergillosis.
Main Methods:
- Phenotypic analysis of a prtT deletion mutant (prtTΔ).
- Assessment of protein utilization as a nutritional source by the mutant.
- Virulence testing of the mutant in a leukopenic mouse model.
Main Results:
- PrtT regulates the expression of several major extracellular proteases in Aspergillus fumigatus.
- The prtTΔ mutant exhibited impaired ability to utilize protein as a nutritional source.
- Virulence of the prtTΔ mutant was not attenuated in the leukopenic mouse model, suggesting secreted proteases may not significantly impact pulmonary aspergillosis.
Conclusions:
- PrtT is a key regulator of secreted protease expression and protein assimilation in Aspergillus fumigatus.
- The study challenges the significant impact of secreted proteases on the virulence of Aspergillus fumigatus in pulmonary aspergillosis.
- Further research is needed to elucidate the precise mechanisms of Aspergillus fumigatus pathogenesis.
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