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Genome-wide functional analysis of phosphatases in the pathogenic fungus Cryptococcus neoformans
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 Authours
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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 & Yong-Sun Bahn |
| Title |
Genome-wide functional analysis of phosphatases in the pathogenic fungus Cryptococcus neoformans |
| Journal |
NAT COMMUN, 2020 (11) ~ |
Abstract
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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. |
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