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

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 RAP), laccase production (LAC1), and the alpha 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.