Biophysical experiments reveal a protective role of protein phosphatase Z1 against oxidative damage of the cell membrane in Candida albicans.

Protein phosphatase Z1 (Ppz1) has been shown to take part in important physiological functions in fungi including a contribution to virulence of Candida albicans. Although its involvement in the oxidative stress response has also been documented, the exact mechanism of action of its protective effect against oxidative damage remains unknown. By developing a pipeline to analyze the biophysical properties of the cell membrane in fungi, we demonstrate that the plasma membrane of Ppz1-KO Candida albicans displays increased sensitivity to tert-butyl-hydroperoxide-induced oxidative damage. In particular, the response to the oxidizing agent, characterized by increased lipid peroxidation, reduced lipid order, and inhibited lateral mobility of plasma membrane components, is significantly more pronounced in the Ppz1-KO C. albicans strain than in the wild-type counterpart. Remarkably, membrane constituents became almost completely immobile in the phosphatase deletion mutant exposed to oxidative stress. Furthermore, moderately elevated membrane lipid peroxidation accompanied by the aforementioned changes in the biophysical characteristics of the plasma membrane are already detectable in untreated Ppz1-KO cells indicating latent membrane damage even in the absence of oxidative stress. In conclusion, the hypersensitivity of cells lacking Ppz1 to oxidative damage establishes that potential Ppz1 inhibitors may synergize with oxidizing agents in prospective anti-fungal combination therapies. [Display omitted] • Membrane damage induced by the oxidizing agent tBOOH is exacerbated in PPZ1 KO Candida albicans. • This damage involves increased membrane hydration and lipid peroxidation as well as lower mobility of membrane components. • Similar biophysical changes can be detected in untreated KO cells implying latent oxidative damage in the KO strain. • The combined effect of the oxidizing agent and the KO genotype immobilized fluorescent lipid markers in the membrane. • Combination of prospective Ppz1 inhibitors with oxidative stress may tackle infections by drug-resistant Candida species. [ABSTRACT FROM AUTHOR]