Aspergillus fumigates is an important pathogen of the immunocompromised host, causing pneumonia and invasive disseminated disease. We have tried to identify factors which contribute to conidial survival in the host, which is essential for causing disease. An A. fumigates mutant strain (white, W), lacking conidial pigmentation, was isolated by UV-mutagenesis. Scanning-EM revealed the surface morphology to be different from that of the wild type (WT). Luminol-dependent chemiluminescence was ten-fold higher when human neutrophils or monocytes were challenged with W conidia, compared to WT conidia. In addition, W conidia were more efficiently damaged by monocytes in vitro and they were more sensitive to attack by oxidants in vitro. In a murine mouse model the W mutants exhibited reduced virulence. A genomic cosmid library was used to clone a gene complementing the W phenotype. Because it encodes a putative polyketide synthase, it was designated pksP (polyketide synthase involved in pigment biosynthesis). The W mutant complemented with pksP displayed all the WT characteristics, indicating that the conidial pigment is of major importance for virulence.
Fungal Genet. Newsl. 46 (Supl):
Full conference title:
Fungal Genetics Conference 20th
- Fungal Genetics Conference 20th (1999)