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Transcription factor PrtT controls expression of multiple secreted proteases in the human pathogenic mold Aspergillus

Haim Sharon1, Shelly Hagag, Nir Osherov

  • 1Department of Human Microbiology, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv 69978, Tel-Aviv, Israel.

Infection and Immunity
|July 1, 2009
PubMed

Insights

The transcription factor PrtT controls secreted proteases in Aspergillus fumigatus, but its deletion did not affect fungal virulence in mice, suggesting PrtT is not a major virulence factor.

Area of Science:

  • Medical Mycology
  • Molecular Biology
  • Fungal Pathogenesis

Background:

  • Secreted proteases are implicated in the virulence of the pathogenic fungus Aspergillus fumigatus, but their precise role is debated.
  • The transcription factor PrtT in Aspergillus niger regulates the expression of multiple secreted proteases.

Purpose of the Study:

  • To investigate the function of the PrtT homolog in Aspergillus fumigatus.
  • To determine the role of PrtT in regulating secreted protease activity and fungal virulence.

Main Methods:

  • Cloning of the A. fumigatus prtT gene.
  • Construction and analysis of an A. fumigatus prtT deletion mutant strain.
  • Assays for secreted protease activity, gene expression, cell killing, erythrocyte lysis, and mouse lung infection models.

Main Results:

  • Deletion of prtT abolished secreted protease activity in A. fumigatus.
  • The expression of six specific secreted proteases was significantly reduced in the prtT deletion mutant.
  • Culture filtrates from the prtT deletion strain showed reduced lung epithelial cell killing and erythrocyte lysis.
  • The prtT deletion strain did not exhibit altered virulence in a mouse model of lung infection.

Conclusions:

  • PrtT is a key regulator of secreted protease expression in Aspergillus fumigatus.
  • Despite regulating protease activity and exhibiting reduced in vitro cytotoxicity, PrtT is not essential for A. fumigatus virulence in a murine lung infection model.

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