Killing of Caenorhabditis elegans by Cryptococcus neoformans as a model of yeast pathogenesis

Eleftherios Mylonakis, Frederick M. Ausubel, John R. Perfect, Joseph Heitman, Stephen B. Calderwood

Research output: Contribution to journalArticlepeer-review

246 Scopus citations

Abstract

We found that the well-studied nematode Caenorhabditis elegans can use various yeasts, including Cryptococcus laurentii and Cryptococcus kuetzingii, as a sole source of food, producing similar brood sizes compared with growth on its usual laboratory food source Escherichia coli OP50. C. elegans grown on these yeasts had a life span similar to (C. laurentii) or longer than (C. kuetzingii) those fed on E. coli. However, the human pathogenic yeast Cryptococcus neoformans killed C. elegans, and the C. neoformans polysaccharide capsule as well as several C. neoformans genes previously shown to be involved in mammalian virulence were also shown to play a role in C. elegans killing. These included genes associated with signal transduction pathways (GPA1, PKA1, PKR1, and RAS1), laccase production (LAC1), and the α mating type. C. neoformans adenine auxotrophs, which are less virulent in mammals, were also less virulent in C. elegans. These results support the model that mammalian pathogenesis of C. neoformans may be a consequence of adaptations that have evolved during the interaction of C neoformans with environmental predators such as free-living nematodes and amoebae and suggest that C. elegans can be used as a simple model host in which C. neoformans pathogenesis can be readily studied.

Original languageEnglish (US)
Pages (from-to)15675-15680
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number24
DOIs
StatePublished - Nov 26 2002

ASJC Scopus subject areas

  • General

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