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 ␣ 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.

Melanin as a virulence factor of Paracoccidioides brasiliensis and other dimorphic pathogenic fungi: a minireview

“…Melanized C. neoformans is more resistant to ingestion by environmental amoeboid [25] or nematode [26] species. Melanins also protect fungi from hydrolytic enzymes [27], UV, solar or gamma radiation [28,29], extreme temperatures [30], and heavy metals and several other toxic compounds [reviewed in 24].…”

GMP Synthase Is Required for Virulence Factor Production and Infection by Cryptococcus neoformans

“…Evaluation of virulence was first performed in the nematode Caenorhabditis elegans, a natural predator of C. neoformans (64). Nematodes were introduced onto a lawn of wild-type, gua1⌬, or gua1⌬ϩGUA1 cells grown on rich brainheart infusion (BHI) medium, minimal nematode growth medium (NGM), and minimal NGM supplemented with 1 mM guanine.…”

Animal Models for Salmonella Pathogenesis: Studies on the Virulence Properties Using Caenorhabditis elegans as a Model Host

“…The standard laboratory food, i.e. E. coli OP50 and Cryptococcus laurentii Garsin et al, 2001;Mylonakis et al, 2002) does not colonize wild-type C. elegans, but various pathogens do. For example, Enterococcus faecalis, a gram-positive bacteria, colonizes in C. elegans and kills very rapidly (Garsin et al, 2001).…”

“…With continued exposure, the worms gradually cease pharyngeal pumping, become immobile, and eventually die. Moreover, large quantities of live bacteria like Salmonella enterica, Burkholderia cepacia, Serratia marcescens, Staphylococcus aureus, Vibrio vulnificus, V. cholerae, and C. neoformans are known to kill worms by colonization (Aballay et al, 2000;Garsin et al, 2001;Mylonakis et al, 2002;Kothe et al, 2003;Kurz et al, 2003;Rhee et al, 2006;Vaitkevicius et al, 2006). A screen of 960 transposon insertions in S. enterica produced 15 mutations with reduced killing of C. elegans, of which only some were virulent (Tenor et al, 2004).…”