TY - JOUR
T1 - A regulator of Aspergillus fumigatus extracellular proteolytic activity is dispensable for virulence
AU - Bergmann, Anna
AU - Hartmann, Thomas
AU - Cairns, Timothy
AU - Bignell, Elaine M.
AU - Krappmann, Sven
PY - 2009/9
Y1 - 2009/9
N2 - 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 eIF2α kinase signaling. Phenotypic classification of a prtTΔ 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. Copyright © 2009, American Society for Microbiology. All Rights Reserved.
AB - 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 eIF2α kinase signaling. Phenotypic classification of a prtTΔ 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. Copyright © 2009, American Society for Microbiology. All Rights Reserved.
U2 - 10.1128/IAI.00425-09
DO - 10.1128/IAI.00425-09
M3 - Article
C2 - 19564390
SN - 1098-5522
VL - 77
SP - 4041
EP - 4050
JO - Infection and immunity
JF - Infection and immunity
IS - 9
ER -