Copper- and zinc-containing superoxide dismutase (Cu/ZnSOD) is required for the protection of Candida albicans against oxidative stresses and the expression of its full virulence

Microbiology. 2002 Nov;148(Pt 11):3705-3713. doi: 10.1099/00221287-148-11-3705.

Abstract

Copper- and zinc-containing superoxide dismutase (Cu/ZnSOD) is suspected to be one of the anti-oxidant enzymes and virulence determinants active in some pathogenic micro-organisms. To elucidate the role of Cu/ZnSOD in the major human fungal pathogen Candida albicans, its gene, designated SOD1, was disrupted by the URA-blaster technique. The resulting sod1/sod1 mutant showed delayed hyphal growth on Spider medium but could still form hyphae on other solid media or in liquid media, particularly in response to serum. Moreover, the sod1/sod1 mutant was more sensitive to menadione, a redox-cycling agent, than the isogenic wild-type strain, although it still showed an adaptive oxidative stress response. Furthermore, the sod1/sod1 mutant cells exhibited slow growth in minimal medium when compared to the wild-type cells, but their growth was restored by the addition of lysine to the medium. Interestingly, C. albicans cells lacking Cu/ZnSOD showed increased susceptibility to macrophage attack and had attenuated virulence in mice. Thus, these results suggest that Cu/ZnSOD is required for the protection of C. albicans against oxidative stresses and for the full virulence of the organism to be expressed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Biological
  • Animals
  • Candida albicans / drug effects
  • Candida albicans / enzymology*
  • Candida albicans / growth & development
  • Candida albicans / pathogenicity
  • Candidiasis / microbiology
  • Disease Models, Animal
  • Humans
  • Lysine / metabolism
  • Macrophages / enzymology
  • Macrophages / microbiology
  • Mice
  • Mice, Inbred BALB C
  • Mutation
  • Oxidative Stress / physiology
  • Protective Agents / metabolism*
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism*
  • Superoxide Dismutase / pharmacology
  • Superoxide Dismutase-1
  • Virulence
  • Vitamin K 3 / pharmacology

Substances

  • Protective Agents
  • SOD1 protein, human
  • Vitamin K 3
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • Lysine