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- Alcohol dehydrogenase 1 and NAD(H)-linked methylglyoxal oxidoreductase reciprocally regulate glutathione-dependent enzyme activities in Candida albicans
- Sa-Ouk Kang , Min-Kyu Kwak
- J. Microbiol. 2021;59(1):76-91. Published online December 23, 2020
- DOI: https://doi.org/10.1007/s12275-021-0552-7
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Abstract
- Glutathione reductase (Glr1) activity controls cellular glutathione and reactive oxygen species (ROS). We previously demonstrated two predominant methylglyoxal scavengers– NAD(H)-linked methylglyoxal oxidoreductase (Mgd1) and alcohol dehydrogenase 1 (Adh1)–in glutathione-depleted γ- glutamyl cysteinyl synthetase-disrupted Candida albicans. However, experimental evidence for Candida pathophysiology lacking the enzyme activities of Mgd1 and Adh1 on glutathione- dependent redox regulation remains unclear. Herein, we have aimed to demonstrate that glutathione-dependent enzyme activities coupled with cellular ROS changes is regulated by methylglyoxal accumulation in Δmgd1/Δadh1 double disruptants. Δmgd1/Δadh1 showed severe growth defects and G1-phase cell cycle arrest. The observed complementary and reciprocal methylglyoxal-oxidizing and methylglyoxalreducing activities between Δmgd1 and Δadh1 were not always exhibited in Δmgd1/Δadh1. Although intracellular accumulation of methylglyoxal and pyruvate was shown in all disruptants, to a greater or lesser degree, methylglyoxal was particularly accumulated in the Δmgd1/Δadh1 double disruptant. While cellular ROS significantly increased in Δmgd1 and Δadh1 as compared to the wild-type, Δmgd1/Δadh1 underwent a decrease in ROS in contrast to Δadh1. Despite the experimental findings underlining the importance of the undergoing unbalanced redox state of Δmgd1/Δadh1, glutathione- independent antioxidative enzyme activities did not change during proliferation and filamentation. Contrary to the significantly lowered glutathione content and Glr1 enzyme activity, the activity staining-based glutathione peroxidase activities concomitantly increased in this mutant. Additionally, the enhanced GLR1 transcript supported our results in Δmgd1/Δadh1, indicating that deficiencies of both Adh1 and Mgd1 activities stimulate specific glutathione-dependent enzyme activities. This suggests that glutathione-dependent redox regulation is evidently linked to C. albicans pathogenicity under the control of methylglyoxal-scavenging activities.
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