Identification of the genes associated with pathogenicity in Aspergillus species: Aspergillus is one of the serious opportunistic fungal pathogens that cause systemic infection in immunocompromised patients especially those with prolonged neutropenia and chronic granulomatous disease from childhood. Aspergillosis is caused by inhaled conidia which is covered with layers of hydrophobic proteins. Two genes, RODA and DEWA, responsible for the spore coat- protein formation have been cloned from Aspergillus nidulans and one of the genes, RODA, was cloned from A. fumigatus. In the previous year, we have shown that binding of fibrinogen and complement C3 are significantly impaired in spores which lack these proteins due to the disruption of genes RODA and DEWA. This year we studied the effect of these genes in virulence using a mouse model. Virulence of the disruptant strain in cortisone immunosupressed mice was found to be significantly reduced when compared to the wild type strain. We have also cloned the ARP1 gene encoding a greenish-blue pigment in spores of Aspergillus fumigatus that modulates complement activation. The ARP1 gene was found to be developmentally regulated since it is expressed during sporulation but not in the earlier stages of the life cycle. The C3 binding assay showed that the wild type strain and the APR1 gene complemented strain have decreased C3 binding than the strain with a mutant ARP1 gene. These results indicate that hydrophobins and the bluish-green pigment of spores play important roles in the pathogenicity of Aspergillus species.
| Ibrahim, Ashraf S; Gebremariam, Teclegiorgis; Liu, Mingfu et al. (2008) Bacterial endosymbiosis is widely present among zygomycetes but does not contribute to the pathogenesis of mucormycosis. J Infect Dis 198:1083-90 |
| Sugui, Janyce A; Chang, Yun C; Kwon-Chung, K J (2005) Agrobacterium tumefaciens-mediated transformation of Aspergillus fumigatus: an efficient tool for insertional mutagenesis and targeted gene disruption. Appl Environ Microbiol 71:1798-802 |
| Chang, Yun C; Tsai, Huei-Fung; Karos, Marvin et al. (2004) THTA, a thermotolerance gene of Aspergillus fumigatus. Fungal Genet Biol 41:888-96 |
| Tsai, H F; Fujii, I; Watanabe, A et al. (2001) Pentaketide melanin biosynthesis in Aspergillus fumigatus requires chain-length shortening of a heptaketide precursor. J Biol Chem 276:29292-8 |
