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Research Paper |
Laboratory of Biophysics, School of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul 151-742, Republic of Korea1
Author for correspondence: Sa-Ouk Kang. Tel: +82 2 880 6703. Fax: +82 2 888 4911. e-mail: kangsaou{at}plaza.snu.ac.kr
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.
Keywords: SOD1, hyphal growth, lysine auxotrophy, candidiasis
Abbreviations: Cu/ZnSOD, copper- and zinc-containing SOD; FeSOD, iron-containing SOD; MnSOD, manganese-containing SOD; ROS, reactive oxygen species; SG, synthetic glucose; SGU, SG plus 25µg uridine ml-1; SOD, superoxide dismutase
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