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Fungal kinases and transcription factors regulating brain infection in Cryptococcus neoformans

Author

Listed:
  • Kyung-Tae Lee

    (Yonsei University)

  • Joohyeon Hong

    (Yonsei University)

  • Dong-Gi Lee

    (Yonsei University)

  • Minjae Lee

    (Yonsei University)

  • Suyeon Cha

    (Yonsei University)

  • Yu-Gyeong Lim

    (Yonsei University)

  • Kwang-Woo Jung

    (Korea Atomic Energy Research Institute)

  • Areum Hwangbo

    (Yonsei University)

  • Yelin Lee

    (Yonsei University)

  • Shang-Jie Yu

    (National Taiwan University
    National Health Research Institute)

  • Ying-Lien Chen

    (National Taiwan University)

  • Jong-Seung Lee

    (AmtixBio Co., Ltd.)

  • Eunji Cheong

    (Yonsei University)

  • Yong-Sun Bahn

    (Yonsei University)

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.

Suggested Citation

  • 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 & Yon, 2020. "Fungal kinases and transcription factors regulating brain infection in Cryptococcus neoformans," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15329-2
    DOI: 10.1038/s41467-020-15329-2
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