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

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 redoxcycling 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.

Superoxide radical induces sclerotial differentiation in filamentous phytopathogenic fungi: a superoxide dismutase mimetics study

“…Moreover, it was found that a manganese-type SOD-encoding gene is upregulated during conidiogenesis of the plant-pathogenic fungus Colletotrichum graminicola (Fang et al, 2002), and Candida albicans, lacking the SOD gene, showed delayed hyphal growth necessary for the full virulence of the organism to be expressed (Hwang et al, 2002). …”

Superoxide dismutases and glutaredoxins have a distinct role in the response of Candida albicans to oxidative stress generated by the chemical compounds menadione and diamide

“…However, while sod1Δ is hypersensitive to killing by a macrophage cell line in vitro (Hwang et al 2002), the same was not observed for sod5Δ (Martchenko et al 2004), indicating that the virulence role of Sod5 may be due to a resistance to different phagocytic cells. Frohner et al (2009) recently demonstrated that the Sod4 and Sod5 produced by innate immune response cells are extremely important as ROS scavengers.…”

“…As mentioned, previous studies have demonstrated that the SOD1 gene and GRX2 gene play a role in the virulence of C. albicans (Hwang et al 2002, Chaves et al 2007). When separately disrupted, these genes led to an attenuation of virulence in an animal model of systemic infection.…”

“…The C. albicans Δsod1 mutant has been shown to be attenuated in virulence in an animal model of systemic infection (Hwang et al 2002, Chaves et al 2007) and more susceptible to macrophage (Hwang et al 2002) and PMN killing (Chaves et al 2007). The mitochondrial Sod2 of C. albicans has been ruled out as a putative virulence factor, but the Δsod2 mutant is more sensitive to heating, ethanol and high concentrations of salts, indicating no direct role in virulence, but a function in different environmental stresses (Hwang et al 2003).…”

“…Some genes related to oxidative stress are also regulated during hyphae formation and appear to be somehow related to C. albicans morphogenesis (Hwang et al 2002, Nantel et al 2002, Martchenko et al 2004, Chaves et al 2007). In addition, Schroter et al (2000) analysed the amount of ROS produced when cells were incubated in 10% serum.…”