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Alcohol dehydrogenase 1 and NAD(H)-linked methylglyoxal oxidoreductase reciprocally regulate glutathione-dependent enzyme activities in Candida albicans

  • Microbial Physiology and Biochemistry
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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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Acknowledgments

We thank W.A. Fonzi, M. Whiteway and G.R. Fink for providing the C. albicans strains and plasmids. This work was supported by the Research Fellowship of the BK21plus project.

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  1. Sa-Ouk Kang

    Present address: Present address: Irwee Institute, B-503, Seongnam, 13510, Republic of Korea

Authors and Affiliations

  1. Laboratory of Biophysics, School of Biological Sciences, and Institute of Microbiology, Seoul National University, Seoul, 08826, Republic of Korea

    Sa-Ouk Kang

  2. Department of Food and Nutrition, Institute of Food and Nutrition Science, Eulji University, Seongnam, 13135, Republic of Korea

    Min-Kyu Kwak

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  1. Sa-Ouk Kang
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The research was designed by M.-K.K., and S.-O. K. The experiments were performed by M.-K.K. Data analysis was performed by M.-K.K., and S.-O. K. New reagents/analytic tools were provided by M.-K.K. The paper was written by M.-K.K.

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Correspondence to Sa-Ouk Kang or Min-Kyu Kwak.

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The authors declare that they have no competing interests.

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Kang, SO., Kwak, MK. Alcohol dehydrogenase 1 and NAD(H)-linked methylglyoxal oxidoreductase reciprocally regulate glutathione-dependent enzyme activities in Candida albicans. J Microbiol. 59, 76–91 (2021). https://doi.org/10.1007/s12275-021-0552-7

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