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Superoxide dismutase influences the virulence of Cryptococcus neoformans by affecting growth within macrophages.

Publication ,  Journal Article
Cox, GM; Harrison, TS; McDade, HC; Taborda, CP; Heinrich, G; Casadevall, A; Perfect, JR
Published in: Infect Immun
January 2003

Superoxide dismutase (SOD) is an enzyme that converts superoxide radicals into hydrogen peroxide and molecular oxygen and has been shown to contribute to the virulence of many human-pathogenic bacteria through its ability to neutralize toxic levels of reactive oxygen species generated by the host. SOD has also been speculated to be important in the pathogenesis of fungal infections, but the role of this enzyme has not been rigorously investigated. To examine the contribution of SOD to the pathogenesis of fungal infections, we cloned the Cu,Zn SOD-encoding gene (SOD1) from the human-pathogenic yeast Cryptococcus neoformans and made mutants via targeted disruption. The sod1 mutant strains had marked decreases in SOD activity and were strikingly more susceptible to reactive oxygen species in vitro. A sod1 mutant was significantly less virulent than the wild-type strain and two independent reconstituted strains, as measured by cumulative survival in the mouse inhalational model. In vitro studies established that the sod1 strain had attenuated growth compared to the growth of the wild type and a reconstituted strain inside macrophages producing reduced amounts of nitric oxide. These findings demonstrate that (i) the Cu,Zn SOD contributes to virulence but is not required for pathogenicity in C. neoformans; (ii) the decreased virulence of the sod1 strain may be due to increased susceptibility to oxygen radicals within macrophages; and (iii) other antioxidant defense systems in C. neoformans can compensate for the loss of the Cu,Zn SOD in vivo.

Duke Scholars

Published In

Infect Immun

DOI

ISSN

0019-9567

Publication Date

January 2003

Volume

71

Issue

1

Start / End Page

173 / 180

Location

United States

Related Subject Headings

  • Virulence
  • Superoxide Dismutase
  • Sequence Analysis, DNA
  • Molecular Sequence Data
  • Microbiology
  • Mice
  • Macrophages, Alveolar
  • Humans
  • Female
  • Cryptococcus neoformans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Cox, G. M., Harrison, T. S., McDade, H. C., Taborda, C. P., Heinrich, G., Casadevall, A., & Perfect, J. R. (2003). Superoxide dismutase influences the virulence of Cryptococcus neoformans by affecting growth within macrophages. Infect Immun, 71(1), 173–180. https://doi.org/10.1128/IAI.71.1.173-180.2003
Cox, Gary M., Thomas S. Harrison, Henry C. McDade, Carlos P. Taborda, Garrett Heinrich, Arturo Casadevall, and John R. Perfect. “Superoxide dismutase influences the virulence of Cryptococcus neoformans by affecting growth within macrophages.Infect Immun 71, no. 1 (January 2003): 173–80. https://doi.org/10.1128/IAI.71.1.173-180.2003.
Cox GM, Harrison TS, McDade HC, Taborda CP, Heinrich G, Casadevall A, et al. Superoxide dismutase influences the virulence of Cryptococcus neoformans by affecting growth within macrophages. Infect Immun. 2003 Jan;71(1):173–80.
Cox, Gary M., et al. “Superoxide dismutase influences the virulence of Cryptococcus neoformans by affecting growth within macrophages.Infect Immun, vol. 71, no. 1, Jan. 2003, pp. 173–80. Pubmed, doi:10.1128/IAI.71.1.173-180.2003.
Cox GM, Harrison TS, McDade HC, Taborda CP, Heinrich G, Casadevall A, Perfect JR. Superoxide dismutase influences the virulence of Cryptococcus neoformans by affecting growth within macrophages. Infect Immun. 2003 Jan;71(1):173–180.

Published In

Infect Immun

DOI

ISSN

0019-9567

Publication Date

January 2003

Volume

71

Issue

1

Start / End Page

173 / 180

Location

United States

Related Subject Headings

  • Virulence
  • Superoxide Dismutase
  • Sequence Analysis, DNA
  • Molecular Sequence Data
  • Microbiology
  • Mice
  • Macrophages, Alveolar
  • Humans
  • Female
  • Cryptococcus neoformans