Functional analysis of genes from Aspergillus fumigatus regulated by the transcription factor CrzA

Abstract

Aspergillus fumigatus is an important opportunistic pathogen. Spores of this fungus are inhaled and reach the lung due to their small size. In the alveoli they become active and germinate. In the immunocompetent host, the phagocytes fungus attack and remove this early stage of infection. In immunosuppressed patients, however, some fungal cells can survive and form hyphae, which is able to infiltrate the surrounding tissue and finally spread to different organs. In opportunistic fungi such as A. fumigatus, the most important genetic components to the establishment of infection are transcription factors that can activate different programs for the regulation of virulence and pathogenicity. Calcineurin is a central signaling molecule in most eukaryotic cells and many of these activities are dependent on the transcription factor CrzA, which becomes transcriptionally active following its dephosphorylation by calcineurin. In many pathogenic fungi, including A. fumigatus, several signaling pathways dependent on the calcineurin-CrzA must be activated during the adaptive process in the mammalian host. Therefore, the importance of the calcineurin-CrzA pathway in the disease induction is critical, and thus the processes regulated by this transcription factor are potential targets antifungals. In our laboratory, we have a large amount of microarray hybridization data from in vitro and in vivo for the mutants ”calA and ”crzA. These data, combined with a chip-seq CrzA could provide a wide base for the identification of genes which have their mRNA accumulation modulated by CrzA. Thus, the functional analysis of genes regulated by this transcription factor may provide a better understanding of this important signal transduction pathway related to virulence and fungal infection.