title: The alkaline protease of Aspergillus fumigatus is not a virulence determinant in two murine models of invasive pulmonary aspergillosis.
abstract: Little is known of the pathophysiology of invasive pulmonary aspergillosis (IPA), an opportunistic fungal infection usually caused by Aspergillus fumigatus. It has been suggested that the ability of the fungus to degrade elastin may aid its invasion and growth in lung tissue. We have described previously the construction of a strain of A. fumigatus in which the gene encoding an alkaline protease, AFAlp, had been disrupted (C.M. Tang, J. Cohen, and D.W. Holden, Mol. Microbiol. 6:1663-1671, 1992); this mutant is deficient in extracellular proteolytic and elastinolytic activity over a broad pH range. In this study, we compared the pathogenicity of this and another AFAlp disruptant with their isogenic, elastase-producing parental strains in two murine models of IPA. In both models, animals were inoculated via the respiratory tract. In the first model, the inoculum was delivered as airborne conidia and animals developed signs of respiratory distress within 2 to 4 days. In the second model, conidia were administered intranasally as a suspension and the disease developed over a 2-week period. No difference was observed between the wild-type and AFAlp disruptants in terms of mortality, and elastin breakdown was detected in lung tissue from animals inoculated with all four strains. We conclude that AFAlp is not a virulence determinant in these models of IPA.
authors: Department of Infectious Diseases and Bacteriology, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
authors: C M
authors: CM
authors: Tang
authors: J
authors: J
authors: Cohen
authors: T
authors: T
authors: Krausz
authors: S
authors: S
authors: Van Noorden
authors: D W
authors: DW
authors: Holden
mesh_terms: D000818:Animals; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000201:enzymology* / Q000382:microbiology / Q000473:pathology; D001232:Aspergillus fumigatus / Q000201:enzymology / Q000472:pathogenicity*; D001483:Base Sequence; D004549:Elastin / Q000378:metabolism; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*
chemical_list: D009838:Oligodeoxyribonucleotides; D004549:Elastin; D010450:Endopeptidases; D012697:Serine Endopeptidases; C026109:oryzin