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Eukaryotic Cell, August 2004, p. 1028-1035, Vol. 3, No. 4
1535-9778/04/$08.00+0     DOI: 10.1128/EC.3.4.1028-1035.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Mutation of the Regulator of G Protein Signaling Crg1 Increases Virulence in Cryptococcus neoformans

Ping Wang,1,2,3* Jim Cutler,1,2,3 Jill King,3 and Daniel Palmer3

Departments of Pediatrics,1 Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center,2 Research Institute for Children, New Orleans, Louisiana3

Received 14 April 2004/ Accepted 8 June 2004

The regulator of G protein signaling homolog Crg1 was found to be a key regulator of pheromone-responsive mating in the opportunistic human fungal pathogen Cryptococcus neoformans. A mutation in the CRG1 gene has greatly increased virulence in the prevalently distributed MAT{alpha} strains of the fungus. Mouse survival time was shortened by 40%, and the lethal dosage was 100-fold less than that of wild-type strains. In addition, the increased virulence of crg1 mutant strains was dependent on the transcription factor homolog Ste12{alpha} but not on the mitogen-activated protein kinase homolog Cpk1. The enhanced mating due to CRG1 mutation, however, was still dependent on Cpk1. Interestingly, crg1 mutants of MAT{alpha} cells produced dark melanin pigment under normally inhibitory conditions, which may relate to the mechanism for increased virulence.


* Corresponding author. Mailing address: Department of Pediatrics, Research Institute for Children, Children's Hospital, 200 Henry Clay Ave., New Orleans, LA 70118. Phone: (504) 896 2739. Fax: (504) 894-5379. E-mail: pwang{at}chnola-research.org.


Eukaryotic Cell, August 2004, p. 1028-1035, Vol. 3, No. 4
1535-9778/04/$08.00+0     DOI: 10.1128/EC.3.4.1028-1035.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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