Systematic functional analysis of kinases in the fungal pathogen Cryptococcus neoformans.

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Lee, K-T; So, Y-S; Yang, D-H; Jung, K-W; Choi, J; Lee, D-G; Kwon, H; Jang, J; Wang, LL; Cha, S; Meyers, GL; Jeong, E; Jin, J-H; Lee, Y; Hong, J; Bang, S; Ji, J-H; Park, G; Byun, H-J; Park, SW; Park, Y-M; Adedoyin, G; Kim, T; Averette, AF; Choi, J-S; Heitman, J; Cheong, E; Lee, Y-H; Bahn, Y-S

Published Date

  • September 28, 2016

Published In

Volume / Issue

  • 7 /

Start / End Page

  • 12766 -

PubMed ID

  • 27677328

Pubmed Central ID

  • 27677328

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/ncomms12766

Language

  • eng

Conference Location

  • England