Molecular dissection of the genes involved in A. fumigatus spore color synthesis and their role in virulence. Aspergillus is one of the most common fungal pathogens affecting neutropenic patients and other types of immunocompromised individuals such as those with Chronic granulomatous Disease of Childhood. Among a dozen species of Aspergillus reported to cause infection in humans, A. fumigatus is the most common species reported from invasive aspergillosis. All Aspergillus species propagate by conidia (spores), which humans encounter daily through inhalation. We have focused our attention on the molecular genetic aspects of conidial pigment biosynthesis since pigment is one of the visible components of the wall that protect conidia. In the previous years we have characterized six developmentally associated genes involved in pentaketide melanin synthesis which are clustered within a 19kb fragment of A. fumigatus genomic DNA. Furthermore, we have shown that the conidial pigment synthetic pathway plays an important role in pathogenesis. Past year we have identified the product of one of the six clustered gene, AYG1, a novel protein, Ayg1p, which shortens the length of the polyketide carbon skeleton from that of a heptaketide to pentaketide. This year the protein is being purified.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000657-10
Application #
6508514
Study Section
(LCI)
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2001
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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