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 () and Yong-Sun Bahn ()
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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
Ying-Lien Chen: National Taiwan University
Jong-Seung Lee: AmtixBio Co., Ltd.
Eunji Cheong: Yonsei University
Yong-Sun Bahn: Yonsei University

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-15329-2

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