A regulator of Aspergillus fumigatus extracellular proteolytic activity is dispensable for virulence.
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.
Bergmann
Anna
A
Research Center for Infectious Diseases, Julius-Maximilians-University, Würzburg, Germany.
Hartmann
Thomas
T
Cairns
Timothy
T
Bignell
Elaine M
EM
Krappmann
Sven
S
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
D005656:Fungal Proteins; D014157:Transcription Factors; D010447:Peptide Hydrolases