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Cryptococcus neoformans mitochondrial superoxide dismutase: an essential link between antioxidant function and high-temperature growth.

Publication ,  Journal Article
Giles, SS; Batinic-Haberle, I; Perfect, JR; Cox, GM
Published in: Eukaryot Cell
January 2005

Manganese superoxide dismutase is an essential component of the mitochondrial antioxidant defense system of most eukaryotes. In the present study, we used a reverse-genetics approach to assess the contribution of the Cryptococcus neoformans manganese superoxide dismutase (Sod2) for antioxidant defense. Strains with mutations in the SOD2 gene exhibited increased susceptibility to oxidative stress as well as poor growth at elevated temperatures compared to isogenic wild-type strains. The sod2Delta mutants were also avirulent in a murine model of inhaled cryptococcosis. Reconstitution of a sod2Delta mutant restored Sod2 activity, eliminated the oxidative stress and temperature-sensitive (ts) phenotypes, and complemented the virulence phenotype. Characterization of the ts phenotype revealed a dependency between Sod2 antioxidant activity and the ability of C. neoformans cells to adapt to growth at elevated temperatures. The ts phenotype could be suppressed by the addition of either ascorbic acid (10 mM) or Mn salen (200 muM) at 30 degrees C, but not at 37 degrees C. Furthermore, sod2Delta mutant cells that were incubated for 24 h at 37 degrees C under anaerobic, but not aerobic, conditions were viable when shifted to the permissive conditions of 25 degrees C in the presence of air. These data suggest that the C. neoformans Sod2 is a major component of the antioxidant defense system in this human fungal pathogen and that adaptation to growth at elevated temperatures is also dependent on Sod2 activity.

Duke Scholars

Published In

Eukaryot Cell

DOI

ISSN

1535-9778

Publication Date

January 2005

Volume

4

Issue

1

Start / End Page

46 / 54

Location

United States

Related Subject Headings

  • Virulence
  • Temperature
  • Superoxide Dismutase
  • Polymerase Chain Reaction
  • Phenotype
  • Oxygen
  • Oxidative Stress
  • Mutation
  • Models, Genetic
  • Mitochondria
 

Citation

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Giles, S. S., Batinic-Haberle, I., Perfect, J. R., & Cox, G. M. (2005). Cryptococcus neoformans mitochondrial superoxide dismutase: an essential link between antioxidant function and high-temperature growth. Eukaryot Cell, 4(1), 46–54. https://doi.org/10.1128/EC.4.1.46-54.2005
Giles, Steven S., Ines Batinic-Haberle, John R. Perfect, and Gary M. Cox. “Cryptococcus neoformans mitochondrial superoxide dismutase: an essential link between antioxidant function and high-temperature growth.Eukaryot Cell 4, no. 1 (January 2005): 46–54. https://doi.org/10.1128/EC.4.1.46-54.2005.
Giles, Steven S., et al. “Cryptococcus neoformans mitochondrial superoxide dismutase: an essential link between antioxidant function and high-temperature growth.Eukaryot Cell, vol. 4, no. 1, Jan. 2005, pp. 46–54. Pubmed, doi:10.1128/EC.4.1.46-54.2005.

Published In

Eukaryot Cell

DOI

ISSN

1535-9778

Publication Date

January 2005

Volume

4

Issue

1

Start / End Page

46 / 54

Location

United States

Related Subject Headings

  • Virulence
  • Temperature
  • Superoxide Dismutase
  • Polymerase Chain Reaction
  • Phenotype
  • Oxygen
  • Oxidative Stress
  • Mutation
  • Models, Genetic
  • Mitochondria