BASIC STUDIES ON ASPERGILLUS SPECIES

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Abstract

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. This year we have identified the product of one of the six clustered gene, AYG1, whos function was unknown. The gene product was found to be a novel protein, Ayg1p, which shortens the length of the polyketide carbon skeleton from that of a heptaketide to pentaketide. In addition, heterologous expression system using A. oryzae, we confirmed that Ayg1p convert heptaketide to pentaketide.