Cryptococcus neoformans Kin1 protein kinase homologue, identified through a Caenorhabditis elegans screen, promotes virulence in mammals.

Published

Journal Article

Cryptococcal infections are a global cause of significant morbidity and mortality. Recent studies support the hypothesis that virulence of Cryptococcus neoformans may have evolved via survival selection in environmental hosts, such as amoebae and free-living nematodes. We used killing of the nematode Caenorhabditis elegans by C. neoformans as an assay to screen a library of random C. neoformans insertion mutants. Of 350 mutants tested, seven were identified with attenuated virulence that persisted after crossing the mutation back into a wild-type strain. Genetic analysis of one strain revealed an insertion in a gene homologous to Saccharomyces cerevisiae KIN1, which encodes a serine/threonine protein kinase. C. neoformans kin1 mutants exhibited significant defects in virulence in murine inhalation and haematogenous infection models and displayed increased binding to alveolar and peritoneal macrophages. The kin1 mutant phenotypes were complemented by the wild-type KIN1 gene. These findings show that the C. neoformans Kin1 kinase homologue is required for full virulence in disparate hosts and that C. elegans can be used as a substitute host to identify novel factors involved in fungal pathogenesis in mammals.

Full Text

Duke Authors

Cited Authors

  • Mylonakis, E; Idnurm, A; Moreno, R; El Khoury, J; Rottman, JB; Ausubel, FM; Heitman, J; Calderwood, SB

Published Date

  • October 2004

Published In

Volume / Issue

  • 54 / 2

Start / End Page

  • 407 - 419

PubMed ID

  • 15469513

Pubmed Central ID

  • 15469513

International Standard Serial Number (ISSN)

  • 0950-382X

Digital Object Identifier (DOI)

  • 10.1111/j.1365-2958.2004.04310.x

Language

  • eng

Conference Location

  • England