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Systematic functional analysis of kinases in the fungal pathogen Cryptococcus neoformans

Cited 45 time in Web of Science Cited 45 time in Scopus
Authors
Lee, Kyung-Tae; So, Yee-Seul; Yang, Dong-Hoon; Jung, Kwang-Woo; Choi, Jaeyoung; Lee, Dong-Gi; Kwon, Hyojeong; Jang, Juyeong; Wang, Li Li; Cha, Soohyun; Meyers, Gena Lee; Jeong, Eunji; Jin, Jae-Hyung; Lee, Yeonseon; Hong, Joohyeon; Bang, Soohyun; Ji, Je-Hyun; Park, Goun; Byun, Hyo-Jeong; Park, Sung Woo; Park, Young-Min; Adedoyin, Gloria; Kim, Taeyup; Averette, Anna F.; Choi, Jong-Soon; Heitman, Joseph; Cheong, Eunji; Lee, Yong-Hwan; Bahn, Yong-Sun
Issue Date
2016-09-28
Publisher
NATURE PUBLISHING GROUP
Citation
NATURE COMMUNICATIONS Vol.7, pp. 12766
Keywords
Systematic functional analysis of kinases in the fungal pathogen Cryptococcus neoformans자연과학
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.
ISSN
2041-1723
Language
English
URI
http://hdl.handle.net/10371/116883
DOI
https://doi.org/10.1038/ncomms12766
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College of Agriculture and Life Sciences (농업생명과학대학)Dept. of Agricultural Biotechnology (농생명공학부)Journal Papers (저널논문_농생명공학부)
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