Systematic functional analysis of kinases in the fungal pathogen Cryptococcus neoformans.
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.
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Kyung-Tae
KT
Lee
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Yee-Seul
YS
So
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Dong-Hoon
DH
Yang
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Kwang-Woo
KW
Jung
Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Korea.
Jaeyoung
J
Choi
Biological Disaster Analysis Group, Korea Basic Science Institute, Daejeon 34133, Korea.
Dong-Gi
http://orcid.org/0000-0002-6767-9543
DG
Lee
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Hyojeong
H
Kwon
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Juyeong
J
Jang
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Li Li
LL
Wang
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Soohyun
S
Cha
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Gena Lee
GL
Meyers
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Eunji
E
Jeong
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Jae-Hyung
JH
Jin
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Yeonseon
Y
Lee
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Joohyeon
J
Hong
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Soohyun
S
Bang
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Je-Hyun
JH
Ji
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Goun
G
Park
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Hyo-Jeong
HJ
Byun
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Sung Woo
SW
Park
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Young-Min
YM
Park
Departments of Molecular Genetics and Microbiology, Medicine, and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Gloria
G
Adedoyin
Departments of Molecular Genetics and Microbiology, Medicine, and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Taeyup
T
Kim
Departments of Molecular Genetics and Microbiology, Medicine, and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Anna F
AF
Averette
Biological Disaster Analysis Group, Korea Basic Science Institute, Daejeon 34133, Korea.
Jong-Soon
JS
Choi
Departments of Molecular Genetics and Microbiology, Medicine, and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Joseph
J
Heitman
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Eunji
E
Cheong
Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Korea.
Yong-Hwan
YH
Lee
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Yong-Sun
http://orcid.org/0000-0001-9573-5752
YS
Bahn
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