S-nitrosoglutathione Enhances H₂O₂ Tolerance in Aspergillus nidulans Conidia

Nitric oxide (NO) and hydrogen peroxide (H₂O₂) are two reactive antimicrobial molecules produced by the immune system, each possessing distinct cytotoxic properties. While their combined presence is generally believed to enhance antimicrobial efficacy, evidence suggests that certain animal and plant cells, as well as bacteria, can counteract this effect by utilizing NO to rapidly mitigate oxidative damage. However, the role of NO in modulating H₂O₂ resistance in filamentous fungi has not been extensively studied. In this study, we investigated the effect of the NO donor S-nitrosoglutathione (GSNO) on the H₂O₂ resistance of Aspergillus nidulans conidia. We found that GSNO pre-treatment significantly enhanced the survival rate of dormant conidia under 2 mmol/L H₂O₂ exposure, while having no effect on swollen conidia or hyphae. Through knockout and phenotypic analysis of key oxidative stress resistance genes, we identified peroxiredoxin (PrxA) as a critical mediator of this enhanced resistance. Further biochemical analyses revealed that GSNO pre-treatment promoted the reduction of disulfide bonds in PrxA dimers, leading to a decrease in intracellular PrxA dimer levels under H₂O₂ stress. This modification reduced PrxA-mediated H₂O₂ decomposition, thereby conserving intracellular reducing power and redirecting cellular resources toward repairing oxidative damage to proteins and DNA. Our findings provide novel insights into the protective mechanisms employed by fungal conidia to withstand oxidative stress and highlight a previously unrecognized role of NO in fungal stress adaptation.