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Examining the early transcriptome of the fungal pathogen Aspergillus fumigatus in response to iron limitation imposed by human serum

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(Thesis) M.Sc.
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Aspergillus fumigatus is an opportunistic fungal pathogen that causes life-threatening invasive aspergillosis (IA) in immunocompromised individuals. Previous studies have shown that iron acquisition by siderophores is required for virulence. We investigated the early transcriptional responseof A. fumigatus to human serum iron limitation via microarray analysis. At 2, 4, or 6 hours post inoculation, 173, 771, or 477 genes were significantly up- or down-regulated, respectively. Under iron limitation, several stress response genes were upregulated, including bZip AP-1, a homolog of the Schizosaccharomyces pombe stress response transcriptional activator PAP1. Mapping the microarray expression data to a Saccharomyces cerevisiae transcriptional regulation network revealed that the FHL1 homolog in A. fumigatus may upregulate the cross-pathway-control transcriptional activator CpcA, a gene that has been previously linked to virulence in A. fumigatus. In conclusion, this study has identified a large number of candidate genes whose expression is altered by human serum iron limitation.
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