Systematic functional analysis of kinases in the fungal pathogen Cryptococcus neoformans.
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.
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Journal articlePermalink
https://hdl.handle.net/10161/13057Published Version (Please cite this version)
10.1038/ncomms12766Publication Info
Lee, Kyung-Tae; So, Yee-Seul; Yang, Dong-Hoon; Jung, Kwang-Woo; Choi, Jaeyoung; Lee,
Dong-Gi; ... Bahn, Yong-Sun (2016). Systematic functional analysis of kinases in the fungal pathogen Cryptococcus neoformans.
Nat Commun, 7. pp. 12766. 10.1038/ncomms12766. Retrieved from https://hdl.handle.net/10161/13057.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Joseph Heitman
Chair, Department of Molecular Genetics and Microbiology
Joseph Heitman was an undergraduate at the University of Chicago (1980-1984), graduating
from the BS-MS program with dual degrees in chemistry and biochemistry with general
and special honors. He then matriculated as an MD-PhD student at Cornell and Rockefeller
Universities and worked with Peter Model and Norton Zinder on how restriction enzymes
recognize specific DNA sequences and how bacteria respond to and repair DNA breaks
and nicks. Dr. Heitman moved as an EMBO long-term fellow to the Bi

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