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Updated: Dec 24, 2025

Biolistic Transformation of a Fluorescent Tagged Gene into the Opportunistic Fungal Pathogen Cryptococcus neoformans
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Biolistic Transformation of a Fluorescent Tagged Gene into the Opportunistic Fungal Pathogen Cryptococcus neoformans

Published on: March 19, 2015

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Fungal kinases and transcription factors regulating brain infection in Cryptococcus neoformans

Kyung-Tae Lee1, Joohyeon Hong1, Dong-Gi Lee1

  • 1Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Korea.

Nature Communications
|April 7, 2020
PubMed

Insights

The fungal transcription factor Hob1 is crucial for Cryptococcus neoformans to infect the brain. It regulates key genes enabling blood-brain barrier crossing and survival during meningoencephalitis.

Area of Science:

  • Mycology
  • Infectious Diseases
  • Neuroscience

Background:

  • Cryptococcus neoformans is a major cause of fatal fungal meningoencephalitis.
  • Understanding the molecular mechanisms of fungal brain invasion is critical for developing effective treatments.

Purpose of the Study:

  • To investigate the roles of fungal kinases and transcription factors (TFs) in the ability of Cryptococcus neoformans to cross the blood-brain barrier (BBB) and establish brain infection.
  • To identify key regulators of fungal brain infectivity.

Main Methods:

  • Utilized a brain infectivity assay with signature-tagged mutagenesis (STM)-based libraries of kinase and TF mutants in the C. neoformans H99 strain.
  • Employed NanoString technology for in vivo transcriptional profiling of kinases and TFs during host infection.
  • Compared findings with Cryptococcus deuterogattii R265, a non-brain-targeting strain.

Main Results:

  • Identified signaling components essential for BBB adhesion, crossing, and survival within the brain parenchyma.
  • The transcription factors Pdr802, Hob1, and Sre1 were indispensable for infection across all tested conditions.
  • Hob1 demonstrated control over the expression of multiple brain infection-related factors, including inositol transporters, a metalloprotease, PDR802, and SRE1.

Conclusions:

  • Hob1 acts as a master regulator of brain infectivity in C. neoformans.
  • Hob1's specific role in brain infection contrasts with its dispensability for most cellular functions in the non-pathogenic C. deuterogattii R265 strain.
  • These findings highlight specific fungal genetic targets for combating cryptococcal meningoencephalitis.

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