|Kim, Jong Heon|
|Chan, Kathleen - Kathy|
|Cheng, Luisa Wai Wai|
|LAND, KIRKWOOD - University Of The Pacific|
Submitted to: Cogent Food & Agriculture
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/1/2020
Publication Date: 9/24/2020
Citation: Kim, J., Chan, K.L., Tam, C.C., Cheng, L.W., Land, K.M. 2020. Crosstalk between the antioxidant and cell wall integrity systems in fungi by 2-hydroxy-4-methoxybenzaldehyde. Cogent Food & Agriculture. 6:1823593. https://doi.org/10.1080/23311932.2020.1823593.
Interpretive Summary: Current antifungal drugs or fungicides have limited efficacy in treating fungal infections, particularly those caused by resistant pathogens. While high-throughput screenings have been investigated for developing new antifungal agents, defining cellular targets of newly identified antifungal agents is still a time-consuming and costly process. We recently identified that the natural compound 2-hydroxy-4-methoxybenzaldehyde (2H4M) could directly disrupt the fungal cell wall and also induce cellular oxidative stress. Fungal mutants lacking key genes in these systems are highly susceptible to 2H4M. Therefore, redox-active natural compounds such as 2H4M that pose no serious medical and environmental side effects could serve as potent antifungal candidates by targeting cellular antioxidant and cell wall integrity systems.
Technical Abstract: The redox-active benzo analog 2-hydroxy-4-methoxybenzaldehyde (2H4M) could serve as a potent redox-cycler in fungal pathogens by disrupting redox homeostasis or redox-sensitive structures in the cell. Using the model yeast Saccharomyces cerevisiae as a molecular tool, this report determined how 2H4M negatively affects both the antioxidant and cell wall integrity systems of fungi, thus proposing on the crosstalk between these two systems under 2H4M-induced stress. We postulate that the cytosolic oxidative stress signals such as superoxide, etc., triggered by 2H4M is transmitted further to activate the cell wall integrity pathway thus contributing to the maintenance of normal cell wall structure.