Rewiring of signaling networks modulating thermotolerance in the human pathogen Cryptococcus neoformans

Dong Hoon Yang, Kwang Woo Jung, Soohyun Bang, Jang Won Lee, Min Hee Song, Anna Floyd-Averette, Richard A. Festa, Giuseppe Ianiri, Alexander Idnurm, Dennis J. Thiele, Joseph Heitman, Yong Sun Bahn

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Thermotolerance is a crucial virulence attribute for human pathogens, including the fungus Cryptococcus neoformans that causes fatal meningitis in humans. Loss of the protein kinase Sch9 increases C. neoformans thermotolerance, but its regulatory mechanism has remained unknown. Here, we studied the Sch9-dependent and Sch9-independent signaling networks modulating C. neoformans thermotolerance by using genome-wide transcriptome analysis and reverse genetic approaches. During temperature upshift, genes encoding for molecular chaperones and heat shock proteins were upregulated, whereas those for translation, transcription, and sterol biosynthesis were highly suppressed. In this process, Sch9 regulated basal expression levels or induced/repressed expression levels of some temperature-responsive genes, including heat shock transcription factor (HSF1) and heat shock proteins (HSP104 and SSA1). Notably, we found that the HSF1 transcript abundance decreased but the Hsf1 protein became transiently phosphorylated during temperature upshift. Nevertheless, Hsf1 is essential for growth and its overexpression promoted C. neoformans thermotolerance. Transcriptome analysis using an HSF1 overexpressing strain revealed a dual role of Hsf1 in the oxidative stress response and thermotolerance. Chromatin immunoprecipitation demonstrated that Hsf1 binds to the step-type like heat shock element (HSE) of its target genes more efficiently than to the perfect-or gap-type HSE. This study provides insight into the thermotolerance of C. neoformans by elucidating the regulatory mechanisms of Sch9 and Hsf1 through the genome-scale identification of temperature-dependent genes.

Original languageEnglish
Pages (from-to)201-219
Number of pages19
JournalGenetics
Volume205
Issue number1
DOIs
Publication statusPublished - 2017 Jan

Bibliographical note

Funding Information:
This work was supported by National Research Foundation of Korea grants (2015R1A2A1A15055687) from the Ministry of Science, ICT and Future Planning and the Strategic Initiative for Microbiomes in Agriculture and Food funded by Ministry of Agriculture, Food and Rural Affairs(OMAFRA) (916006- 2) (to Y.-S.B.). The work was also supported in part by National Institutes of Health(NIH) grants R21-AI094364 (to A.I.), R37-AI39115-19 and R01-AI50113-12 (to J.H.), R01- GM041840 (to D.J.T.), and F32-GM100678 (to R.A.F.).

All Science Journal Classification (ASJC) codes

  • Genetics

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