Synergism of Antifungal Activity between Mitochondrial Respiration Inhibitors and Kojic Acid

Molecules

Jong H. Kim¹  Bruce C. Campbell¹  Kathleen L. Chan¹  Noreen Mahoney¹ 

[1] Plant Mycotoxin Research Unit, Western Regional Research Center, USDA-ARS, 800 Buchanan St., Albany, CA 94710, USA

关键词: kojic acid;    Aspergillus;    Penicillium;    Acremonium;    Scedosporium;    yeast;    hydrogen peroxide;    mitochondrial respiration inhibitors;    chemosensitization;   

DOI  :  10.3390/molecules18021564

来源: mdpi

【 摘 要 】

Co-application of certain types of compounds to conventional antimicrobial drugs can enhance the efficacy of the drugs through a process termed chemosensitization. We show that kojic acid (KA), a natural pyrone, is a potent chemosensitizing agent of complex III inhibitors disrupting the mitochondrial respiratory chain in fungi. Addition of KA greatly lowered the minimum inhibitory concentrations of complex III inhibitors tested against certain filamentous fungi. Efficacy of KA synergism in decreasing order was pyraclostrobin > kresoxim-methyl > antimycin A. KA was also found to be a chemosensitizer of cells to hydrogen peroxide (H₂O₂), tested as a mimic of reactive oxygen species involved in host defense during infection, against several human fungal pathogens and Penicillium strains infecting crops. In comparison, KA-mediated chemosensitization to complex III inhibitors/H₂O₂ was undetectable in other types of fungi, including Aspergillus flavus,A. parasiticus, and P. griseofulvum, among others. Of note, KA was found to function as an antioxidant, but not as an antifungal chemosensitizer in yeasts. In summary, KA could serve as an antifungal chemosensitizer to complex III inhibitors or H₂O₂ against selected human pathogens or Penicillium species. KA-mediated chemosensitization to H₂O₂ seemed specific for filamentous fungi. Thus, results indicate strain- and/or drug-specificity exist during KA chemosensitization.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.