Cryptococcus neoformans gene involved in mammalian pathogenesis identified by a Caenorhabditis elegans progeny-based approach.
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.
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Related Subject Headings
- Virulence
- Sequence Homology, Nucleic Acid
- Saccharomyces cerevisiae Proteins
- Mutation
- Microbiology
- Mice, Inbred Strains
- Mice
- Guanine Nucleotide Exchange Factors
- Genes, Fungal
- Female
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Virulence
- Sequence Homology, Nucleic Acid
- Saccharomyces cerevisiae Proteins
- Mutation
- Microbiology
- Mice, Inbred Strains
- Mice
- Guanine Nucleotide Exchange Factors
- Genes, Fungal
- Female