|Title:||Fungal kinases and transcription factors regulating brain infection in Cryptococcus neoformans||Authors:||Lee, K.-T.
|Issue Date:||2020||Journal Volume:||11||Journal Issue:||1||Source:||Nature Communications||Abstract:||
Cryptococcus neoformans causes fatal fungal meningoencephalitis. Here, we study the roles played by fungal kinases and transcription factors (TFs) in blood-brain barrier (BBB) crossing and brain infection in mice. We use a brain infectivity assay to screen signature-tagged mutagenesis (STM)-based libraries of mutants defective in kinases and TFs, generated in the C. neoformans H99 strain. We also monitor in vivo transcription profiles of kinases and TFs during host infection using NanoString technology. These analyses identify signalling components involved in BBB adhesion and crossing, or survival in the brain parenchyma. The TFs Pdr802, Hob1, and Sre1 are required for infection under all the conditions tested here. Hob1 controls the expression of several factors involved in brain infection, including inositol transporters, a metalloprotease, PDR802, and SRE1. However, Hob1 is dispensable for most cellular functions in Cryptococcus deuterogattii R265, a strain that does not target the brain during infection. Our results indicate that Hob1 is a master regulator of brain infectivity in C. neoformans. ? 2020, The Author(s).
|DOI:||10.1038/s41467-020-15329-2||metadata.dc.subject.other:||amphotericin B; fluconazole; messenger RNA; phosphotransferase; transcription factor; transcription factor hob; transcription factor sre1; unclassified drug; fungal protein; homeodomain protein; phosphotransferase; transcription factor; adhesion; bioassay; biotechnology; blood; brain; fungus; gene expression; infectivity; laboratory method; mutation; rodent; amino terminal sequence; animal experiment; animal model; animal tissue; antibiotic sensitivity; Article; blood brain barrier; brain infection; brain tissue; comparative study; controlled study; cryptococcosis; female; fungal virulence; in vitro study; in vivo study; melanogenesis; mouse; nonhuman; parenchyma; pathogenicity; RNA transcription; signal transduction; signature-tagged mutagenesis; upregulation; animal; brain; cryptococcal meningitis; Cryptococcus gattii; Cryptococcus neoformans; disease model; gene expression profiling; gene expression regulation; genetics; human; meningoencephalitis; metabolism; microbiology; mutagenesis; mutation; pathology; permeability; Filobasidiella neoformans; Mus; Animals; Blood-Brain Barrier; Brain; Cryptococcus gattii; Cryptococcus neoformans; Disease Models, Animal; Female; Fungal Proteins; Gene Expression Profiling; Gene Expression Regulation, Fungal; Homeodomain Proteins; Humans; Meningitis, Cryptococcal; Meningoencephalitis; Mice; Mutagenesis; Mutation; Permeability; Phosphotransferases; Signal Transduction; Transcription Factors
|Appears in Collections:||植物病理與微生物學系|
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