This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wormley, F. L. Articles by Cox, G. M. Search for Related Content PubMed PubMed Citation Articles by Wormley, F. L., Jr. Articles by Cox, G. M.

Identification and Characterization of an SKN7 Homologue in Cryptococcus neoformans

Duke University Medical Center, Durham, North Carolina 27710

Received 23 November 2004/ Returned for modification 27 December 2004/ Accepted 1 April 2005

Cryptococcus neoformans is an encapsulated fungal pathogen that primarily infects the central nervous system of immunocompromised individuals, causing life-threatening meningoencephalitis. The capacity of C. neoformans to subvert host defenses and disseminate by intracellular parasitism of alveolar macrophages in the immune-compromised host has led to studies to evaluate genes associated with C. neoformans resistance to oxidative stress. In the present study, we identify and characterize a C. neoformans homologue to SKN7, a transcription factor in Saccharomyces cerevisiae that regulates the oxidative stress response, cell cycle, and cell wall biosynthesis. To examine the contribution of SKN7 in the pathogenesis of fungal infections, we created skn7 mutants via targeted disruption. The skn7 mutants were observed to be more susceptible to reactive oxygen species in vitro and were significantly less virulent than the wild-type strain and a reconstituted strain as measured by cumulative survival in the mouse inhalational model. The Skn7 protein was observed to be important for expression of thioredoxin reductase in response to oxidative challenge. Interestingly, skn7 mutants were also observed to flocculate following in vitro culture, a novel phenotype not observed in skn7 mutants derived from other fungi. These findings demonstrate that SKN7 contributes to the virulence composite but is not required for pathogenicity in C. neoformans. In addition, flocculation of C. neoformans skn7 mutants suggests a potentially unique function of SKN7 not previously observed in other cryptococcal strains or skn7 mutants.

Editor: T. R. Kozel

This article has been cited by other articles:

• Zhao, X., Mehrabi, R., Xu, J.-R. (2007). Mitogen-Activated Protein Kinase Pathways and Fungal Pathogenesis. Eukaryot Cell 6: 1701-1714 [Full Text]  
• Jones, C. A., Greer-Phillips, S. E., Borkovich, K. A. (2007). The Response Regulator RRG-1 Functions Upstream of a Mitogen-activated Protein Kinase Pathway Impacting Asexual Development, Female Fertility, Osmotic Stress, and Fungicide Resistance in Neurospora crassa. Mol. Biol. Cell 18: 2123-2136 [Abstract] [Full Text]  
• Izumitsu, K., Yoshimi, A., Tanaka, C. (2007). Two-Component Response Regulators Ssk1p and Skn7p Additively Regulate High-Osmolarity Adaptation and Fungicide Sensitivity in Cochliobolus heterostrophus. Eukaryot Cell 6: 171-181 [Abstract] [Full Text]  
• Bahn, Y.-S., Kojima, K., Cox, G. M., Heitman, J. (2006). A Unique Fungal Two-Component System Regulates Stress Responses, Drug Sensitivity, Sexual Development, and Virulence of Cryptococcus neoformans. Mol. Biol. Cell 17: 3122-3135 [Abstract] [Full Text]  
• Missall, T. A., Pusateri, M. E., Donlin, M. J., Chambers, K. T., Corbett, J. A., Lodge, J. K. (2006). Posttranslational, Translational, and Transcriptional Responses to Nitric Oxide Stress in Cryptococcus neoformans: Implications for Virulence. Eukaryot Cell 5: 518-529 [Abstract] [Full Text]