title: Global control of dimorphism and virulence in fungi.
abstract: 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.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, WI 53792, USA.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Nemecek
authors.forename: Marcel
authors.initials: M
authors.lastname: Wüthrich
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Klein
mesh_terms: D000818:Animals; D001758:Blastomyces / Q000166:cytology / Q000201:enzymology / Q000235:genetics* / Q000472:pathogenicity*; D001759:Blastomycosis / Q000382:microbiology; D003045:Coccidioides / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D005816:Genetic Complementation Test; D000071677:Histidine Kinase; D006658:Histoplasma / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity; D006660:Histoplasmosis / Q000382:microbiology; D008172:Lung Diseases, Fungal / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D016366:Open Reading Frames; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D034622:RNA Interference; D012441:Saccharomyces cerevisiae / Q000235:genetics; D012988:Soil Microbiology; D013172:Spores, Fungal / Q000502:physiology; D013696:Temperature; D014774:Virulence / Q000235:genetics
chemical_list: D005656:Fungal Proteins; D011494:Protein Kinases; D000071677:Histidine Kinase