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bioRxiv · 10.1101/2023.09.05.556406

The Candida albicans ζ-crystallin homolog Zta1 promotes resistance to oxidative stress

Gandra, R. M.·Johnson, C. J.·Nett, J. E.·Konopka, J. B.
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Abstract

The fungal pathogen Candida albicans is capable of causing lethal infections in humans. Its pathogenic potential is due in part to the ability to resist various stress conditions in the host, including oxidative stress. Recent studies showed that a family of four flavodoxin-like proteins (Pst1, Pst2, Pst3, Ycp4) that function as quinone reductases promotes resistance to oxidation and is needed for virulence. Therefore, in this study Zta1 was examined because it belongs to a structurally distinct family of quinone reductases that are highly conserved in eukaryotes and have been called the {zeta}-crystallins. The levels of Zta1 in C. albicans rapidly increased after exposure to oxidants, consistent with a role in resisting oxidative stress. Accumulation of reactive oxygen species was significantly higher in cells lacking ZTA1 upon exposure to quinones and other oxidants. Furthermore, deletion of ZTA1 in a mutant lacking the four flavodoxin-like proteins, resulted in further increased susceptibility to quinones, indicating that these distinct quinone reductases work in combination. These results demonstrate that Zta1 contributes to C. albicans survival after exposure to oxidative conditions, which increases the understanding of how C. albicans resists stressful conditions in the host. IMPORTANCECandida albicans is an important human pathogen that can cause lethal systemic infections. The ability of C. albicans to colonize and establish infections is closely tied to its highly adaptable nature and capacity to resist various types of stress, including oxidative stress. Previous studies showed that four C. albicans proteins belonging to the flavodoxin-like protein family of quinone reductases are needed for resistance to quinones and for virulence. Therefore, in this study we examined the role of a distinct type of quinone reductase, Zta1, and found that it acts in conjunction with the flavodoxin-like proteins to protect against oxidative stress.

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Gandra, R. M., Johnson, C. J., Nett, J. E., Konopka, J. B.. 2023-09-06. The Candida albicans ζ-crystallin homolog Zta1 promotes resistance to oxidative stress. https://doi.org/10.1101/2023.09.05.556406

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