Genome-wide functional analysis of phosphatases in the pathogenic fungus Cryptococcus neoformans

Jae-Hyung Jin, Kyung-Tae Lee, Joohyeon Hong, Dongpil Lee, Eun-Ha Jang, Jin-Young Kim, Yeonseon Lee, Seung-Heon Lee, Yee-Seul So, Kwang-Woo Jung, Dong-Gi Lee, Eunji Jeong, Minjae Lee, Yu-Byeong Jang, Yeseul Choi, Myung Ha Lee, Ji-Seok Kim, Seong-Ryong Yu, Jin-Tae Choi, Jae-Won La, Haneul Choi, Sun-Woo Kim, Kyung Jin Seo, Yelin Lee, Eun Jung Thak, Jaeyoung Choi, Anna F. Averette, Yong-Hwan Lee, Joseph Heitman, Hyun Ah Kang, Eunji Cheong and Yong-Sun Bahn ()
Additional contact information
Jae-Hyung Jin: Yonsei University
Kyung-Tae Lee: Yonsei University
Joohyeon Hong: Yonsei University
Dongpil Lee: Yonsei University
Eun-Ha Jang: Yonsei University
Jin-Young Kim: Yonsei University
Yeonseon Lee: Yonsei University
Seung-Heon Lee: Yonsei University
Yee-Seul So: Yonsei University
Kwang-Woo Jung: Yonsei University
Dong-Gi Lee: Yonsei University
Eunji Jeong: Yonsei University
Minjae Lee: Yonsei University
Yu-Byeong Jang: Yonsei University
Yeseul Choi: Yonsei University
Myung Ha Lee: Yonsei University
Ji-Seok Kim: Yonsei University
Seong-Ryong Yu: Yonsei University
Jin-Tae Choi: Yonsei University
Jae-Won La: Yonsei University
Haneul Choi: Yonsei University
Sun-Woo Kim: Yonsei University
Kyung Jin Seo: Yonsei University
Yelin Lee: Yonsei University
Eun Jung Thak: Chung-Ang University
Jaeyoung Choi: Korea Institute of Science and Technology
Anna F. Averette: Duke University Medical Center
Yong-Hwan Lee: Seoul National University
Joseph Heitman: Duke University Medical Center
Hyun Ah Kang: Chung-Ang University
Eunji Cheong: Yonsei University
Yong-Sun Bahn: Yonsei University

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: Abstract Phosphatases, together with kinases and transcription factors, are key components in cellular signalling networks. Here, we present a systematic functional analysis of the phosphatases in Cryptococcus neoformans, a fungal pathogen that causes life-threatening fungal meningoencephalitis. We analyse 230 signature-tagged mutant strains for 114 putative phosphatases under 30 distinct in vitro growth conditions, revealing at least one function for 60 of these proteins. Large-scale virulence and infectivity assays using insect and mouse models indicate roles in pathogenicity for 31 phosphatases involved in various processes such as thermotolerance, melanin and capsule production, stress responses, O-mannosylation, or retromer function. Notably, phosphatases Xpp1, Ssu72, Siw14, and Sit4 promote blood-brain barrier adhesion and crossing by C. neoformans. Together with our previous systematic studies of transcription factors and kinases, our results provide comprehensive insight into the pathobiological signalling circuitry of C. neoformans.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18028-0

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DOI: 10.1038/s41467-020-18028-0

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