A. fumigatus, as both saprophytic mould and medically important human pathogen, needs efficient mechanisms to sense environmental signals and transduce them intracellularly to survive in its entirely different habitats. One of these signal transduction pathways is the cAMP dependent protein kinase A (PKA) pathway. For A. fumigatus, components of this generally well conserved signaling cascade have been characterized in detail and its significance for virulence was shown. To identify target genes of PKA, we performed microarray analyses using a mutant strain overproducing the PKA catalytic subunit in comparison to the corresponding wild type. Following this approach, we were able to find 282 up and 343 down regulated genes involved in different cellular processes like carbon and nitrogen metabolism, cell cycle regulation and ribosome biogenesis. Among these genes potentially regulated by PKA, 23 transcription factors were found of which 15 were deleted and the mutant phenotypes were characterized under different cultivation conditions. A C6 finger domain protein that shows highest upregulation of all identified transcription factors is located in a potential secondary metabolite gene cluster. Because a gene deletion resulted only in minor phenotypical changes, an overexpression mutant of this transcription factor was created to gain deeper insights into its function.
Full conference title:
- Asperfest 9 (2012)