Mycobiology.  2014 Mar;42(1):52-58.

A Nudix Hydrolase Protein, Ysa1, Regulates Oxidative Stress Response and Antifungal Drug Susceptibility in Cryptococcus neoformans

• Lee KT
• Kwon H
• Lee D
• Bahn YS

Abstract

A nucleoside diphosphate-linked moiety X (Nudix) hydrolase-like gene, YSA1, has been identified as one of the gromwell plant extract-responsive genes in Cryptococcus neoformans. Ysa1 is known to control intracellular concentrations of ADP-ribose or O-acetyl-ADP-ribose, and has diverse biological functions, including the response to oxidative stress in the ascomycete yeast, Saccharomyces cerevisiae. In this study, we characterized the role of YSA1 in the stress response and adaptation of the basidiomycete yeast, C. neoformans. We constructed three independent deletion mutants for YSA1, and analyzed their mutant phenotypes. We found that ysa1 mutants did not show increased sensitivity to reactive oxygen species-producing oxidative damage agents, such as hydrogen peroxide and menadione, but exhibited increased sensitivity to diamide, which is a thiol-specific oxidant. Ysa1 was dispensable for the response to most environmental stresses, such as genotoxic, osmotic, and endoplasmic reticulum stress. In conclusion, modulation of YSA1 may regulate the cellular response and adaptation of C. neoformans to certain oxidative stresses and contribute to the evolution of antifungal drug resistance.

Keyword

Cryptococcus neoformans; Nudix hydrolase; Oxidative stress; Ysa1

MeSH Terms

Adenosine Diphosphate Ribose
Ascomycota
Basidiomycota
Cryptococcus neoformans*
Cryptococcus*
Diamide
Drug Resistance, Fungal
Endoplasmic Reticulum Stress
Hydrogen Peroxide
Lithospermum
O-Acetyl-ADP-Ribose
Oxidative Stress*
Oxygen
Phenotype
Plants
Saccharomyces cerevisiae
Vitamin K 3
Yeasts
Adenosine Diphosphate Ribose
Diamide
Hydrogen Peroxide
O-Acetyl-ADP-Ribose
Oxygen
Vitamin K 3