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Molecules 2013, 18(2), 1564-1581; doi:10.3390/molecules18021564
Article

Synergism of Antifungal Activity between Mitochondrial Respiration Inhibitors and Kojic Acid

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Received: 4 January 2013 / Revised: 19 January 2013 / Accepted: 22 January 2013 / Published: 25 January 2013
(This article belongs to the Section Metabolites)
Download PDF [559 KB, 18 June 2014; original version 18 June 2014]

Abstract

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.
Keywords: kojic acid; Aspergillus; Penicillium; Acremonium; Scedosporium; yeast; hydrogen peroxide; mitochondrial respiration inhibitors; chemosensitization kojic acid; Aspergillus; Penicillium; Acremonium; Scedosporium; yeast; hydrogen peroxide; mitochondrial respiration inhibitors; chemosensitization
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Kim, J.H.; Campbell, B.C.; Chan, K.L.; Mahoney, N.; Haff, R.P. Synergism of Antifungal Activity between Mitochondrial Respiration Inhibitors and Kojic Acid. Molecules 2013, 18, 1564-1581.

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