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Identification and characterization of an SKN7 homologue in Cryptococcus neoformans.

Publication ,  Journal Article
Wormley, FL; Heinrich, G; Miller, JL; Perfect, JR; Cox, GM
Published in: Infect Immun
August 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.

Duke Scholars

Published In

Infect Immun

DOI

ISSN

0019-9567

Publication Date

August 2005

Volume

73

Issue

8

Start / End Page

5022 / 5030

Location

United States

Related Subject Headings

  • tert-Butylhydroperoxide
  • Virulence
  • Transcription Factors
  • Saccharomyces cerevisiae Proteins
  • Oxidative Stress
  • Organisms, Genetically Modified
  • Mutation
  • Molecular Sequence Data
  • Microbiology
  • Mice
 

Citation

APA
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ICMJE
MLA
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Wormley, F. L., Heinrich, G., Miller, J. L., Perfect, J. R., & Cox, G. M. (2005). Identification and characterization of an SKN7 homologue in Cryptococcus neoformans. Infect Immun, 73(8), 5022–5030. https://doi.org/10.1128/IAI.73.8.5022-5030.2005
Wormley, F. L., G. Heinrich, J. L. Miller, J. R. Perfect, and G. M. Cox. “Identification and characterization of an SKN7 homologue in Cryptococcus neoformans.Infect Immun 73, no. 8 (August 2005): 5022–30. https://doi.org/10.1128/IAI.73.8.5022-5030.2005.
Wormley FL, Heinrich G, Miller JL, Perfect JR, Cox GM. Identification and characterization of an SKN7 homologue in Cryptococcus neoformans. Infect Immun. 2005 Aug;73(8):5022–30.
Wormley, F. L., et al. “Identification and characterization of an SKN7 homologue in Cryptococcus neoformans.Infect Immun, vol. 73, no. 8, Aug. 2005, pp. 5022–30. Pubmed, doi:10.1128/IAI.73.8.5022-5030.2005.
Wormley FL, Heinrich G, Miller JL, Perfect JR, Cox GM. Identification and characterization of an SKN7 homologue in Cryptococcus neoformans. Infect Immun. 2005 Aug;73(8):5022–5030.

Published In

Infect Immun

DOI

ISSN

0019-9567

Publication Date

August 2005

Volume

73

Issue

8

Start / End Page

5022 / 5030

Location

United States

Related Subject Headings

  • tert-Butylhydroperoxide
  • Virulence
  • Transcription Factors
  • Saccharomyces cerevisiae Proteins
  • Oxidative Stress
  • Organisms, Genetically Modified
  • Mutation
  • Molecular Sequence Data
  • Microbiology
  • Mice