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

Synergism of Antifungal Activity between Mitochondrial Respiration Inhibitors and Kojic Acid

* ,
,
,
 and
Received: 4 January 2013; in revised form: 19 January 2013 / Accepted: 22 January 2013 / Published: 25 January 2013
(This article belongs to the Section Metabolites)
Download PDF [559 KB, updated 18 June 2014; original version uploaded 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.

Export to BibTeX |
EndNote


MDPI and ACS Style

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.

AMA Style

Kim JH, Campbell BC, Chan KL, Mahoney N, Haff RP. Synergism of Antifungal Activity between Mitochondrial Respiration Inhibitors and Kojic Acid. Molecules. 2013; 18(2):1564-1581.

Chicago/Turabian Style

Kim, Jong H.; Campbell, Bruce C.; Chan, Kathleen L.; Mahoney, Noreen; Haff, Ronald P. 2013. "Synergism of Antifungal Activity between Mitochondrial Respiration Inhibitors and Kojic Acid." Molecules 18, no. 2: 1564-1581.


Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert