title: A regulator of Aspergillus fumigatus extracellular proteolytic activity is dispensable for virulence.
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.
authors: Research Center for Infectious Diseases, Julius-Maximilians-University, Würzburg, Germany.
authors: Anna
authors: A
authors: Bergmann
authors: Thomas
authors: T
authors: Hartmann
authors: Timothy
authors: T
authors: Cairns
authors: Elaine M
authors: EM
authors: Bignell
authors: Sven
authors: S
authors: Krappmann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001232:Aspergillus fumigatus / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity*; D002478:Cells, Cultured; D005656:Fungal Proteins / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000502:physiology*; D014774:Virulence
chemical_list: D005656:Fungal Proteins; D014157:Transcription Factors; D010447:Peptide Hydrolases