title: Cryptococcus neoformans gene involved in mammalian pathogenesis identified by a Caenorhabditis elegans progeny-based approach.
abstract: Caenorhabditis elegans can serve as a substitute host for the study of microbial pathogenesis. We found that mutations in genes of the fungal pathogen Cryptococcus neoformans involved in mammalian virulence allow C. elegans to produce greater numbers of progeny than when exposed to wild-type fungus. We used this property to screen a library of C. neoformans mutants for strains that permit larger C. elegans brood sizes. In this screen, we identified a gene homologous to Saccharomyces cerevisiae ROM2. C. neoformans rom2 mutation resulted in a defect in mating and growth defects at elevated temperature or in the presence of cell wall or hyperosmolar stresses. An effect of the C. neoformans rom2 mutation in virulence was confirmed in a murine inhalation infection model. We propose that a screen for progeny-permissive mutants of microorganisms can serve as a high-throughput method for identifying novel loci related to mammalian pathogenesis.
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Gray-Jackson 504, 55 Fruit Street, Boston, MA 02114, USA.
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Tang
authors.forename: Julia
authors.initials: J
authors.lastname: Breger
authors.forename: Alexander
authors.initials: A
authors.lastname: Idnurm
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Gerik
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Lodge
authors.forename: Joseph
authors.initials: J
authors.lastname: Heitman
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Calderwood
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Mylonakis
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000382:microbiology*; D003453:Cryptococcosis / Q000382:microbiology*; D003455:Cryptococcus neoformans / Q000235:genetics* / Q000472:pathogenicity*; D005260:Female; D005800:Genes, Fungal; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D014774:Virulence / Q000235:genetics
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C490929:ROM2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins