Aspergillus fumigatus is a saprophytic fungus that can invade immuno-compromised patients through the lung and disseminates via the bloodstream. There is little known about how the fungus can regulate its gene expression to adapt to harsh conditions in blood. We are searching for genes that are up-regulated during blood infection. To study this process we designed an in vitro model to investigate the transcriptome of the fungus. In this setting mycelium is incubated in blood and then analyzed in microarray, transcriptome sequencing and quantitative Realtime-PCR. Differentially expressed genes were identified. Functional enrichment analysis revealed that at a late stage during blood incubation genes are up-regulated in the FunCat categories virulence, disease factors, toxins and detoxification by degradation. During early time points of blood incubation we detect up- regulated genes that belong to a family of regulators in filamentous fungi. The velvet gene family consists of the four proteins veA, velB, velC, and vosA, which exhibit regulatory functions during development in Aspergillus nidulans. Together with laeA, the velvet proteins seem to undergo various interactions in A. nidulans in order to respond to changed environmental conditions and stress. These features make them interesting candidates for involvement in the adaption process of A. fumigatus in blood. Functional deletions of velB, velC, vosA, and laeA were generated and characterized and will be studied in the in vitro blood model.
Full conference title:
- Asperfest 9 (2012)