Transcriptional networks controlling virulence in filamentous fungal pathogens

Dissemination through the bloodstream represents a critical step in systemic fungal infection. How filamentous fungi are able to survive in the hostile environment of human blood is largely unknown. The TRANSPAT project integrates genetic and transcriptomic approaches to generate a high-resolution map of the fungal transcriptome during growth in human blood. The aim is to define transcriptional networks of clinical relevance in Aspergillus and Fusarium, two important human pathogens. Using two complementary approaches, custom oligoarrays and massively parallel sequencing of cDNA (RNA-seq), genome wide expression profiles were generated during early stages of blood growth, leading to the identification of hundreds of genes whose transcript levels are significantly upregulated in Aspergillus and Fusarium during growth on human blood. In the Austrian subproject, key virulence transcription factors such as the iron regulator HapX, the CCAAT-binding complex (CBC, also termed Hap complex), the pH regulator PacC and the sulfur regulator MetR were identified and/or characterized. Transcriptome analysis of mutants deficient in these transcription factors provided new insights into the genetic programmes that determine virulence of filamentous fungal pathogens, facilitating the identification of novel antifungal targets and suggesting new antifungal treatment options.