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Infection and Immunity, December 2005, p. 8219-8225, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.8219-8225.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Cryptococcus neoformans Gene Involved in Mammalian Pathogenesis Identified by a Caenorhabditis elegans Progeny-Based Approach

Robin J. Tang,1 Julia Breger,1 Alexander Idnurm,2 Kimberly J. Gerik,3 Jennifer K. Lodge,3,4 Joseph Heitman,2,6,7,8 Stephen B. Calderwood,1,5 and Eleftherios Mylonakis1*

Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts 02114,1 Department of Molecular Genetics and Microbiology,2 Division of Infectious Diseases,6 Department of Medicine,7 Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710,8 Edward A. Doisy Department of Biochemistry and Molecular Biology,3 Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, Missouri 63104,4 Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 021145

Received 2 August 2005/ Returned for modification 10 September 2005/ Accepted 21 September 2005

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.

* Corresponding author. Mailing address: Massachusetts General Hospital, Gray-Jackson 504, 55 Fruit Street, Boston, MA 02114. Phone: (617) 726-3811. Fax: (617) 726-7416. E-mail: emylonakis{at}partners.org.

Editor: A. Casadevall

Infection and Immunity, December 2005, p. 8219-8225, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.8219-8225.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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