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.
Department of Infectious Diseases and Bacteriology, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
J M
JM
Smith
C M
CM
Tang
S
S
Van Noorden
D W
DW
Holden
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