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[The role of virulence factor of elastolytic proteinase from Aspergillus fumigatus]
Y Hasegawa1, T Nikai, Y Shibata
1Department of Microbiology, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tenpaku-ku, Nagoya 468-8503, Japan.
Abstract:
The role of virulence factor of elastolytic proteinase produced by Aspergillus fumigatus was investigated in mice immunocompromised with cyclophosphamide (CY) to block neutrophil and lymphocyte functions or with carrageenan (CA) to block the phagocytic activity of macrophages. These mice were infected through inhalation with the spores of elastolytic proteinase producing or nonproducing strains of A. fumigatus, and then were observed daily for 15 days or until death. Compared to CY-immunocompromised mice treated with the spores of proteinase nonproducing strains, CY-immunocompromised mice treated with the spores of proteinase producing strains had a significantly shorter survival rate. Furthermore, when treated with the spores of proteinase producing strains, CA-immunocompromised mice survived significantly longer than did CY-immunocompromised mice. Assessment of the effect of elastolytic proteinase on rat lung showed that this enzyme induced hemorrhage of the lung, alveolar septal edema and alveolar hypertrophy due to blood neutrophil infiltration. Neither fusion nor denaturation of the elastic fiber was observed, however. These studies have suggested that when infected with A. fumigatus, a severe lesion in bronchioli or alveoli is induced by the proteinase producing strains, and that these strains are more virulent than the proteinase nonproducing strains.
Insights
Aspergillus fumigatus elastolytic proteinase producing strains are more virulent, causing severe lung lesions and reduced survival in immunocompromised mice. This virulence factor plays a key role in invasive pulmonary aspergillosis.
Area of Science:
- Medical Mycology
- Pathogen Virulence Factors
- Immunocompromised Host Response
Background:
- Aspergillus fumigatus is an opportunistic fungal pathogen.
- Elastolytic proteinase is a potential virulence factor in A. fumigatus infections.
- Understanding A. fumigatus virulence is crucial for treating invasive aspergillosis.
Purpose of the Study:
- To investigate the role of elastolytic proteinase from Aspergillus fumigatus as a virulence factor.
- To compare the pathogenicity of proteinase-producing and non-producing strains in immunocompromised mice.
- To assess the direct effects of elastolytic proteinase on lung tissue.
Main Methods:
- Mice were immunocompromised using cyclophosphamide (CY) or carrageenan (CA).
- Mice were infected via inhalation with A. fumigatus spores (proteinase-producing or non-producing strains).
- Survival rates were monitored, and lung tissues were examined for pathological changes.
Main Results:
- CY-treated mice infected with proteinase-producing strains had significantly lower survival rates compared to those infected with non-producing strains.
- CA-treated mice infected with proteinase-producing strains survived longer than CY-treated mice.
- Elastolytic proteinase induced lung hemorrhage, edema, and neutrophil infiltration in rats, but did not cause elastic fiber damage.
Conclusions:
- Elastolytic proteinase-producing A. fumigatus strains are more virulent and induce severe lung lesions.
- The proteinase contributes to A. fumigatus pathogenicity, particularly in the context of neutrophil and lymphocyte dysfunction.
- These findings highlight the importance of proteinase activity in invasive pulmonary aspergillosis.