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Infection and Immunity, April 2003, p. 1988-1994, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.1988-1994.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Cryptococcus neoformans with a Mutation in the Tetratricopeptide Repeat-Containing Gene, CCN1, Causes Subcutaneous Lesions but Fails To Cause Systemic Infection

Seyung Chung, Philippe Mondon, Yun C. Chang, and Kyung J. Kwon-Chung*

Molecular Microbiology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892

Received 4 October 2002/ Returned for modification 27 November 2002/ Accepted 2 January 2003

We studied a Cryptococcus neoformans strain that caused feline chronic nasal granuloma without disseminated disease. This strain, B-4551, grows at temperatures up to 35°C and fails to cause systemic infection in mice. Many cells of B-4551 formed short hyphal elements in feline nasal tissue and occasionally at 35°C in vitro. A complementation and sequence analysis revealed that the temperature-sensitive (Ts) phenotype of B-4551 was due to deletion of a lysine residue in the cryptococcal CCN1 gene. B-4551 complemented with the wild type CCN1 gene grew at 37°C and caused fatal systemic infection in mice. The CCN1 gene encodes a protein containing 16 copies of a tetratricopeptide repeat. CCN1 is homologous to the Saccharomyces cerevisiae CLF1 gene, which is required for pre-mRNA splicing, cell cycle progression, and DNA replication, and to the Drosophila melanogaster crn gene, which is involved in neurogenesis. CLF1 complemented the Ts phenotype of B-4551. CCN1, however, failed to rescue the clf1 mutant in S. cerevisiae. These results indicate that the Ccn1p may not be as functionally diverse as Clf1p in yeast.

* Corresponding author. Mailing address: MMS, LCI, NIAID, Bldg. 10, 11C304, National Institutes of Health, Bethesda, MD 20892. Phone: (301) 496-1602. Fax: (301) 402-1003. E-mail: June_Kwon-chung{at}nih.gov.

Editor: T. R. Kozel

Infection and Immunity, April 2003, p. 1988-1994, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.1988-1994.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.





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