title: Killing of Caenorhabditis elegans by Cryptococcus neoformans as a model of yeast pathogenesis.
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 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.
authors.affiliation: Division of Infectious Diseases and Department of Molecular Biology, Massachusetts General Hospital, Boston 02114, USA.
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Mylonakis
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Ausubel
authors.forename: John R
authors.initials: JR
authors.lastname: Perfect
authors.forename: Joseph
authors.initials: J
authors.lastname: Heitman
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Calderwood
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000382:microbiology*; D003454:Cryptococcus; D003455:Cryptococcus neoformans / Q000235:genetics / Q000472:pathogenicity*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004195:Disease Models, Animal; D004926:Escherichia coli; D005247:Feeding Behavior; D016166:Free Radical Scavengers; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics; D005800:Genes, Fungal; D049770:Genes, Mating Type, Fungal; D020962:Heterotrimeric GTP-Binding Proteins / Q000502:physiology; D042845:Laccase; D007980:Levodopa / Q000494:pharmacology; D008136:Longevity; D008543:Melanins / Q000096:biosynthesis; D010088:Oxidoreductases / Q000502:physiology; D011134:Polysaccharides / Q000502:physiology; D015398:Signal Transduction; D013045:Species Specificity; D014774:Virulence
chemical_list: D016166:Free Radical Scavengers; D005656:Fungal Proteins; D008543:Melanins; D011134:Polysaccharides; D007980:Levodopa; D010088:Oxidoreductases; D042845:Laccase; D017868:Cyclic AMP-Dependent Protein Kinases; D020962:Heterotrimeric GTP-Binding Proteins