The Transcriptome of Pathogenic Aspergillus Fumigatus

Institute For Genomic Research, Rockville MD

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Abstract

DESCRIPTION (provided by applicant): Aspergillus fumigatus is a prevalent mold growing on the nonliving organic materials in the soil. This organism in the air disperses non-sexual spores called conidia. While most Aspergilli are harmless to humans, exposure to A. fumigatus can cause an allergic response in sensitive individuals. More importantly, A. fumigatus is an opportunistic pathogen causing invasive disease in bone marrow transplant patients, AIDS patients, and other immune compromised individuals. The genome sequencing of Aspergillus fumigatus is currently in progress at TIGR and elsewhere. Shotgun sequencing has proceeded to 10-fold genome coverage providing the sequence for nearly all of the estimated 10,000 genes in the genome. The sequencing project will be finished in 2003. To date fewer than 100 genes have been cloned and their function analysed in A. fumigatus, and fewer than 750 in all Aspergilli. Understanding gene function, even with the genome sequence will take many decades unless large-scale genome-based biological experiments can be done. Current approaches to understanding the pathobiology of the organism using mutants with single or double gene disruption have been unrewarding. Many genes are duplicated with close homologues rendering the gene disruption strategy inefficient and unsuited to this organism, which undoubtedly has multiple virulence traits compared with other Aspergilli. The hypothesis of this proposal is that patterns of gene expression revealed by microarray analysis will provide insight into growth, virulence mechanisms, cell death and antifungal drug resistance in A. fumigatus. We will construct a whole genome glass slide microarray from PCR products representing each ORF in the genome. This microarray will be used in a series of experiments to explore the biology and pathogenicity of this organism. Whole genome ORF specific microarray analysis will provide the first global means of looking at gene expression patterns in this organism and will reveal the activities of multiple genes whose products are involved in pathogenicity and allergenicity in humans.