Global Control of Dimorphism and Virulence in Fungi

• DOI: 10.1126/science.1124105
• Publication Date: 2006-04-27T21:18:09Z
• Authors: Julie C. Nemecek; Marcel Wüthrich; Bruce S. Klein
• Keywords: Coccidioides; Histidine Kinase; Lung Diseases, Fungal; Genes, Fungal; Genetic Complementation Test; Histoplasma; Molecular Sequence Data; Saccharomyces cerevisiae; 02 engineering and technology; Blastomycosis; Fungal Proteins; Mice, Inbred C57BL; Mice; Mutagenesis, Insertional; Open Reading Frames; Gene Expression Regulation, Fungal; Blastomyces; Animals; RNA Interference; 0210 nano-technology; Histoplasmosis; Protein Kinases

Microbial pathogens that normally inhabit our environment can adapt to thrive inside mammalian hosts. There are six dimorphic fungi that cause disease worldwide, which switch from nonpathogenic molds in soil to pathogenic yeast after spores are inhaled and exposed to elevated temperature. Mechanisms that regulate this switch remain obscure. We show that a hybrid histidine kinase senses host signals and triggers the transition from mold to yeast. The kinase also regulates cell-wall integrity, sporulation, and expression of virulence genes in vivo. This global regulator shapes how dimorphic fungal pathogens adapt to the mammalian host, which has broad implications for treating and preventing systemic fungal disease.