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United States Department of Agriculture

Agricultural Research Service

Research Project: Chemical Approaches to Eliminate Fungal Contamination and Mycotoxin Production in Plant Products

Location: Foodborne Toxin Detection and Prevention

Title: Synergism of antifungal activity between mitochondrial respiration inhibitors and kojic acid

Authors
item Kim, Jong Heon
item Campbell, Bruce -
item Chan, Kathleen
item Mahoney, Noreen
item Haff, Ronald

Submitted to: Molecules
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 22, 2013
Publication Date: January 25, 2013
Repository URL: http://doi:10.3390/molecules18021564
Citation: Kim, J.H., Campbell, B.C., Chan, K.L., Mahoney, N.E., Haff, R.P. 2013. Synergism of antifungal activity between mitochondrial respiration inhibitors and kojic acid. Molecules. 18:1564-1581.

Interpretive Summary: Effective control of fungal pathogens occurring in agricultural farms or humans (especially immunocompromised patients) is a continuous problem. Development of resistance to available antifungal drugs results in unremitting searches for new antifungal agents or alternative control methods. In this report, we show that kojic acid, a safe, natural compound, can enhance the antifungal activity of certain commercial antimycotic drugs. Discovery of this synergism is based upon pinpointing vulnerable targets in fungi, namely energy production or antioxidation. Results of this study will ultimately lead to prevention of development of fungal resistance to conventional fungicides, such as strobilurins. It will also lead to lowering costs or dosages of commercial drugs or fungicides necessary for effective control of fungal pathogens.

Technical Abstract: Co-application of certain types of compounds with conventional antimicrobial drugs results in the enhancement of efficacy of drugs through a mechanism termed chemosensitization. We show that kojic acid (KA), a natural product, is a potent chemosensitizer to complex III inhibitors of mitochondrial respiratory chain of fungi. KA greatly lowers minimum inhibitory concentrations of complex III inhibitors, such as strobilurins, against filamentous fungi. KA also functions as a chemosensitizer to hydrogen peroxide (H2O2), which mimics reactive oxygen species involved in host defense during infection, against human pathogens or Penicillium strains infecting crops. KA-mediated chemosensitization to H2O2 seemed specific for filamentous fungi, indicating strain- or drug-specificity exists during chemosensitization. KA could serve as a promising chemosensitizer to complex III inhibitors or H2O2 against certain human pathogens or Penicillium species. Interpretive Summary: Effective control of fungal pathogens occurring in agricultural farms or humans (especially immunocompromised patients) is a continuous problem. Development of resistance to available antifungal drugs results in unremitting searches for new antifungal agents or alternative control methods. In this report, we show that kojic acid, a safe, natural compound, can enhance the antifungal activity of certain commercial antimycotic drugs. Discovery of this synergism is based upon pinpointing vulnerable targets in fungi, namely energy production or antioxidation. Results of this study will ultimately lead to prevention of development of fungal resistance to conventional fungicides, such as strobilurins. It will also lead to lowering costs or dosages of commercial drugs or fungicides necessary for effective control of fungal pathogens.

Last Modified: 9/2/2014
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