Systematic functional analysis of kinases in the fungal pathogen Cryptococcus neoformans

Kyung-Tae Lee, Yee-Seul So, Dong-Hoon Yang, Kwang-Woo Jung, Jaeyoung Choi, Dong-Gi Lee, Hyojeong Kwon, Juyeong Jang, Li Li Wang, Soohyun Cha, Gena Lee Meyers, Eunji Jeong, Jae-Hyung Jin, Yeonseon Lee, Joohyeon Hong, Soohyun Bang, Je-Hyun Ji, Goun Park, Hyo-Jeong Byun, Sung Woo Park, Young-Min Park, Gloria Adedoyin, Taeyup Kim, Anna F. Averette, Jong-Soon Choi, Joseph Heitman, Eunji Cheong, Yong-Hwan Lee and Yong-Sun Bahn ()
Additional contact information
Kyung-Tae Lee: College of Life Science and Biotechnology, Yonsei University
Yee-Seul So: College of Life Science and Biotechnology, Yonsei University
Dong-Hoon Yang: College of Life Science and Biotechnology, Yonsei University
Kwang-Woo Jung: College of Life Science and Biotechnology, Yonsei University
Jaeyoung Choi: Seoul National University
Dong-Gi Lee: Biological Disaster Analysis Group, Korea Basic Science Institute
Hyojeong Kwon: College of Life Science and Biotechnology, Yonsei University
Juyeong Jang: College of Life Science and Biotechnology, Yonsei University
Li Li Wang: College of Life Science and Biotechnology, Yonsei University
Soohyun Cha: College of Life Science and Biotechnology, Yonsei University
Gena Lee Meyers: College of Life Science and Biotechnology, Yonsei University
Eunji Jeong: College of Life Science and Biotechnology, Yonsei University
Jae-Hyung Jin: College of Life Science and Biotechnology, Yonsei University
Yeonseon Lee: College of Life Science and Biotechnology, Yonsei University
Joohyeon Hong: College of Life Science and Biotechnology, Yonsei University
Soohyun Bang: College of Life Science and Biotechnology, Yonsei University
Je-Hyun Ji: College of Life Science and Biotechnology, Yonsei University
Goun Park: College of Life Science and Biotechnology, Yonsei University
Hyo-Jeong Byun: College of Life Science and Biotechnology, Yonsei University
Sung Woo Park: College of Life Science and Biotechnology, Yonsei University
Young-Min Park: College of Life Science and Biotechnology, Yonsei University
Gloria Adedoyin: Medicine, and Pharmacology and Cancer Biology, Duke University Medical Center
Taeyup Kim: Medicine, and Pharmacology and Cancer Biology, Duke University Medical Center
Anna F. Averette: Medicine, and Pharmacology and Cancer Biology, Duke University Medical Center
Jong-Soon Choi: Biological Disaster Analysis Group, Korea Basic Science Institute
Joseph Heitman: Medicine, and Pharmacology and Cancer Biology, Duke University Medical Center
Eunji Cheong: College of Life Science and Biotechnology, Yonsei University
Yong-Hwan Lee: Seoul National University
Yong-Sun Bahn: College of Life Science and Biotechnology, Yonsei University

Nature Communications, 2016, vol. 7, issue 1, 1-16

Abstract: Abstract Cryptococcus neoformans is the leading cause of death by fungal meningoencephalitis; however, treatment options remain limited. Here we report the construction of 264 signature-tagged gene-deletion strains for 129 putative kinases, and examine their phenotypic traits under 30 distinct in vitro growth conditions and in two different hosts (insect larvae and mice). Clustering analysis of in vitro phenotypic traits indicates that several of these kinases have roles in known signalling pathways, and identifies hitherto uncharacterized signalling cascades. Virulence assays in the insect and mouse models provide evidence of pathogenicity-related roles for 63 kinases involved in the following biological categories: growth and cell cycle, nutrient metabolism, stress response and adaptation, cell signalling, cell polarity and morphology, vacuole trafficking, transfer RNA (tRNA) modification and other functions. Our study provides insights into the pathobiological signalling circuitry of C. neoformans and identifies potential anticryptococcal or antifungal drug targets.

Date: 2016
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DOI: 10.1038/ncomms12766

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