Fungal kinases and transcription factors regulating brain infection in Cryptococcus neoformans

Kyung Tae Lee, Joohyeon Hong, Dong Gi Lee, Minjae Lee, Suyeon Cha, Yu Gyeong Lim, Kwang Woo Jung, Areum Hwangbo, Yelin Lee, Shang Jie Yu, Ying Lien Chen, Jong Seung Lee, Eunji Cheong, Yong Sun Bahn

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

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.

Original languageEnglish
Article number1521
JournalNature communications
Volume11
Issue number1
DOIs
Publication statusPublished - 2020 Dec 1

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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