Targeting antioxidative signal transduction and stress response system: control of pathogenic Aspergillus with
J H Kim1, B C Campbell, N Mahoney
1Plant Mycotoxin Research Unit, Western Regional Research Center, USDA-ARS, Albany, CA 94710, USA.
Aims:
The aim of this study was to show whether antioxidative response systems are potentially useful molecular targets for control of Aspergillus fumigatus and Aspergillus flavus. Selected phenolic agents are used in target-gene-based bioassays to determine their impact on mitochondrial respiration.
Methods And Results:
Vanillyl acetone, vanillic acid, vanillin, cinnamic acid, veratraldehyde, m-coumaric acid (phenolic agents to which Saccharomyces cerevisiae sod2delta mutant showed sensitivity), carboxin (inhibits complex II of the mitochondrial respiratory chain), strobilurins/antimycin A (inhibits complex III of the mitochondrial respiratory chain) and fludioxonil/fenpiclonil [antifungals potentiated by mitogen-activated protein kinase (MAPK)] were examined in A. fumigatus, A. flavus and S. cerevisiae. Individual or combined application of phenolics with inhibitors of mitochondrial respiration showed some of the phenolics effectively inhibited fungal growth. Target-gene bioassays were performed using a sakAdelta (MAPK deletion) strain of A. fumigatus and a complementation analysis using the mitochondrial superoxide dismutase (Mn-SOD) gene (sodA) of A. flavus in the ortholog mutant, sod2delta, of S. cerevisiae. The results demonstrated that mitochondrial antioxidative stress system plays important roles in fungal response to antifungal agents tested.
Conclusions:
Antioxidative response systems of fungi can be an efficient molecular target of phenolics for pathogen control. Combined application of phenolics with inhibitors of mitochondrial respiration can effectively suppress the growth of fungi.
Significance And Impact Of The Study:
Natural compounds that do not pose any significant medical or environmental risks could serve as useful alternatives or additives to conventional antifungals. Identifying the antioxidative response systems in other pathogens could improve methods for fungal control.
Insights
Phenolic compounds can target fungal antioxidative systems, inhibiting growth of Aspergillus species. Combining phenolics with mitochondrial respiration inhibitors offers an effective strategy for fungal control, potentially leading to safer alternatives to conventional antifungals.
Area of Science:
- Mycology
- Biochemistry
- Molecular Biology
Background:
- Antioxidative response systems are crucial for fungal survival and virulence.
- Understanding these systems can reveal novel targets for antifungal drug development.
- Aspergillus fumigatus and Aspergillus flavus are significant opportunistic fungal pathogens.
Purpose of the Study:
- To investigate antioxidative response systems as molecular targets for controlling Aspergillus fumigatus and Aspergillus flavus.
- To evaluate the impact of phenolic agents on fungal mitochondrial respiration.
- To determine the efficacy of phenolics, alone or combined with mitochondrial inhibitors, against fungal growth.
Main Methods:
- Phenolic agents and known mitochondrial respiration inhibitors were tested against A. fumigatus, A. flavus, and Saccharomyces cerevisiae.
- Gene-based bioassays were conducted using a mitogen-activated protein kinase (MAPK) deletion strain (sakAΔ) of A. fumigatus.
- Complementation analysis involved the mitochondrial superoxide dismutase (Mn-SOD) gene (sodA) of A. flavus in an S. cerevisiae mutant (sod2Δ).
Main Results:
- Several phenolic agents demonstrated significant inhibition of fungal growth, particularly when combined with mitochondrial respiration inhibitors.
- The study confirmed the role of mitochondrial antioxidative stress systems in fungal response to tested antifungal agents.
- Specific phenolics showed sensitivity in the sod2Δ mutant of S. cerevisiae, indicating targeting of mitochondrial pathways.
Conclusions:
- Fungal antioxidative response systems represent an effective molecular target for phenolic compounds in pathogen control.
- The combined application of phenolics and mitochondrial respiration inhibitors can significantly suppress fungal growth.
- Natural compounds targeting these systems offer potential as safe alternatives or adjuncts to conventional antifungals.
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