Copper-Only Superoxide Dismutase 6 (SOD6) regulates DNA-damage induced virulence in Candida albicans

Superoxide dismutase (SOD) serves as the first line of defense against reactive oxygen species (ROS), protecting organisms from oxidative stress. Recently, a fungal-specific copper-only SOD family was identified in Candida albicans (C. albicans), yet the function of SOD6, a member of this new family, remains unreported. To investigate the function of SOD6 in C. albicans, we constructed the sod6 Δ/Δ mutant strain using transient CRISPR/Cas9 technology. We then found that the sod6 Δ/Δ mutant strain significantly accumulated excessive intracellular and extracellular ROS and showed heightened sensitivity to exogenous oxidants, including H2O2. sod6 Δ/Δ mutant strain displayed increased sensitivity to zeocin, which indicated the strain of sod6 Δ/Δsignificant DNA damage. Additionally, the sod6 Δ/Δ mutant strain exhibited significant decrease in virulence in both Galleria mellonella and murine models of C. albicans infection. Collectively these findings suggest that SOD6 facilitates the DNA damage related virulence of C. albicans, positioning it.

超氧化物歧化酶（Superoxide dismutase, SOD）是机体对抗活性氧（reactive oxygen species, ROS）的第一道防线，可保护生物体免受氧化应激损伤。近期研究在白色念珠菌（Candida albicans, C. albicans）中鉴定出一类真菌特异性仅含铜的SOD家族，而该新家族成员SOD6的功能尚未见报道。为探究白色念珠菌中SOD6的功能，本研究采用瞬时CRISPR/Cas9技术构建了sod6 Δ/Δ突变菌株。研究发现，sod6 Δ/Δ突变菌株胞内与胞外均积累了过量活性氧，且对外源氧化剂（包括过氧化氢H₂O₂）的敏感性显著升高。sod6 Δ/Δ突变菌株对泽古霉素（zeocin）的敏感性增强，提示该菌株存在显著的DNA损伤。此外，sod6 Δ/Δ突变菌株在大蜡螟（Galleria mellonella）与小鼠白色念珠菌感染模型中均表现出毒力显著下降。综上，上述研究结果表明SOD6可促进白色念珠菌与DNA损伤相关的毒力，明确了其功能定位。