Global control of dimorphism and virulence in fungi.
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.
Nemecek
Julie C
JC
Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, WI 53792, USA.
Wüthrich
Marcel
M
Klein
Bruce S
BS
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
D005656:Fungal Proteins; D011494:Protein Kinases; D000071677:Histidine Kinase