Cryptococcus neoformans gene involved in mammalian pathogenesis identified by a Caenorhabditis elegans progeny-based approach

Robin J. Tang, Julia Breger, Alexander Idnurm, Kimberly J. Gerik, Jennifer K. Lodge, Joseph Heitman, Stephen B. Calderwood, Eleftherios Mylonakis

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

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.

Original languageEnglish
Pages (from-to)8219-8225
Number of pages7
JournalInfection and immunity
Volume73
Issue number12
DOIs
StatePublished - Dec 2005

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