Virulence of Aspergillus fumigatus double mutants lacking restriction and an alkaline protease in a low-dose model of invasive pulmonary aspergillosis.
To investigate the pathogenicity of Aspergillus fumigatus mutants lacking putative virulence factors, we have developed a new murine model of invasive pulmonary aspergillosis based on neutropenia, the major factor predisposing patients to this infection. Mice were treated with cyclophosphamide and inoculated by the intranasal route with 5 x 10(3) conidia, a significant reduction from inoculum levels used in previous models. Evidence for the production of the extracellular alkaline protease (Alp) in lung tissue was obtained by using a fungal transformant harboring an alp::lacZ reporter gene fusion. The pathogenicities of single mutant strains lacking either Alp or the ribotoxin restrictocin and of a double mutant strain lacking both proteins were assessed in this infection model. There were no significant differences between the mutant and the wild-type strains in terms of mortality or histological-features. Inoculations with mixtures of conidia showed that the double mutant strain is slightly less virulent than the wild-type strain. We conclude that Alp and restrictocin are not important virulence determinants in pulmonary infection.
Smith
J M
JM
Department of Infectious Diseases and Bacteriology, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
Tang
C M
CM
Van Noorden
S
S
Holden
D W
DW
D000485:Allergens; D000818:Animals; D052179:Antigens, Plant; D001228:Aspergillosis / Q000382:microbiology* / Q000473:pathology; D001232:Aspergillus fumigatus / Q000235:genetics / Q000472:pathogenicity*; D003520:Cyclophosphamide / Q000494:pharmacology; D004195:Disease Models, Animal; D005656:Fungal Proteins / Q000235:genetics*; D008168:Lung / Q000382:microbiology; D008172:Lung Diseases, Fungal / Q000382:microbiology* / Q000473:pathology; D008297:Male; D051379:Mice; D009154:Mutation; D009503:Neutropenia / Q000139:chemically induced; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012260:Ribonucleases; D012697:Serine Endopeptidases / Q000235:genetics*; D016019:Survival Analysis; D014170:Transformation, Genetic
C081947:ASPF1 protein, Aspergillus fumigatus; D000485:Allergens; D052179:Antigens, Plant; D005656:Fungal Proteins; D011993:Recombinant Fusion Proteins; C036196:MITF protein, Aspergillus restrictus; D003520:Cyclophosphamide; D012260:Ribonucleases; D012697:Serine Endopeptidases; C026109:oryzin