{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T13:50:17Z","timestamp":1780321817097,"version":"3.54.1"},"reference-count":35,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2014,11,12]],"date-time":"2014-11-12T00:00:00Z","timestamp":1415750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Oxidative treatment is one of the strategies for preventing Penicillium contamination in crops\/foods. The antifungal efficacy of hydrogen peroxide (H2O2; oxidant) was investigated in Penicillium strains by using kojic acid (KA) as a chemosensitizing agent, which can enhance the susceptibility of pathogens to antifungal agents. Co-application of KA with H2O2 (chemosensitization) resulted in the enhancement of antifungal activity of either compound, when compared to the independent application of each agent alone. Of note, heat enhanced the activity of H2O2 to a greater extent during chemosensitization, whereby the minimum inhibitory or minimum fungicidal concentrations of H2O2 was decreased up to 4 or 13 fold, respectively, at 35\u201345 \u00b0C (heat), when compared to that at 28 \u00b0C (normal growth temperature). However, heat didn\u2019t increase the antifungal activity of KA, indicating specificity exists between heat and types of antifungals applied. The effect of chemosensitization was also strain-specific, where P. expansum (both parental and fludioxonil-resistant mutants) or P. italicum 983 exhibited relatively higher susceptibility to the chemosensitization, comparing to other Penicillium strains tested. Collectively, chemosensitization can serve as a potent antifungal strategy to lower effective dosages of toxic antifungal substances, such as H2O2. This can lead to coincidental lowering of environmental and health risks.<\/jats:p>","DOI":"10.3390\/molecules191118448","type":"journal-article","created":{"date-parts":[[2014,11,12]],"date-time":"2014-11-12T11:53:07Z","timestamp":1415793187000},"page":"18448-18464","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Augmenting the Antifungal Activity of an Oxidizing Agent with Kojic Acid: Control of Penicillium Strains Infecting Crops"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0944-6685","authenticated-orcid":false,"given":"Jong","family":"Kim","sequence":"first","affiliation":[{"name":"Foodborne Toxin Detection and Prevention Research Unit, Western Regional Research Center, USDA-ARS, 800 Buchanan St., Albany, CA 94710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Chan","sequence":"additional","affiliation":[{"name":"Foodborne Toxin Detection and Prevention Research Unit, Western Regional Research Center, USDA-ARS, 800 Buchanan St., Albany, CA 94710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1021\/jf404026f","article-title":"Synthesis, characterization, and antimicrobial activity of kojic acid grafted chitosan oligosaccharide","volume":"62","author":"Liu","year":"2014","journal-title":"J. Agric. Food Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e91259","DOI":"10.1371\/journal.pone.0091259","article-title":"A novel function for kojic acid, a secondary metabolite from Aspergillus fungi, as antileishmanial agent","volume":"9","author":"Rodrigues","year":"2014","journal-title":"PLoS One"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1039\/b603758p","article-title":"From miso, sake and shoyu to cosmetics: A century of science for kojic acid","volume":"23","author":"Bentley","year":"2006","journal-title":"Nat. Prod. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2440","DOI":"10.3390\/ijms10062440","article-title":"An updated review of tyrosinase inhibitors","volume":"10","author":"Chang","year":"2009","journal-title":"Int. J. Mol. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Lajis, A.F., Hamid, M., and Ariff, A.B. (2012). Depigmenting effect of kojic acid esters in hyperpigmented B16F1 melanoma cells. J. Biomed. Biotechnol., 2012.","DOI":"10.1155\/2012\/952452"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1111\/j.1468-3083.2011.04130.x","article-title":"Natural options for the management of hyperpigmentation","volume":"25","author":"Leyden","year":"2011","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1590\/S1517-83822014000100045","article-title":"Modulation of antimicrobial metabolites production by the fungus Aspergillus parasiticus","volume":"45","author":"Bracarense","year":"2014","journal-title":"Braz. J. Microbiol."},{"key":"ref_8","first-page":"89","article-title":"Kojic acid\u2014A new leading molecule for a preparation of compounds with an anti-neoplastic potential","volume":"46","author":"Novotny","year":"1999","journal-title":"Neoplasma"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/BF00917315","article-title":"Kojic acid scavenges free radicals while potentiating leukocyte functions including free radical generation","volume":"15","author":"Niwa","year":"1991","journal-title":"Inflammation"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1042\/CBI20100083","article-title":"Kojic acid, a secondary metabolite from Aspergillus sp., acts as an inducer of macrophage activation","volume":"35","author":"Rodrigues","year":"2011","journal-title":"Cell Biol. Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"248","DOI":"10.4489\/MYCO.2003.31.4.248","article-title":"Fungistatic activity of kojic acid against human pathogenic fungi and inhibition of melanin production in Cryptococcus neoformans","volume":"31","author":"Chee","year":"2003","journal-title":"Mycobiology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s00253-004-1670-y","article-title":"An isolate of Aspergillus flavus used to reduce aflatoxin contamination in cottonseed has a defective polyketide synthase gene","volume":"65","author":"Ehrlich","year":"2004","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3389\/fmicb.2014.00087","article-title":"Use of benzo analogs to enhance antimycotic activity of kresoxim methyl for control of aflatoxigenic fungal pathogens","volume":"5","author":"Kim","year":"2014","journal-title":"Front. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.toxlet.2014.06.847","article-title":"Effects of the mycotoxin patulin at the level of nuclear receptor transcriptional activity and steroidogenesis in vitro","volume":"229","author":"Frizzell","year":"2014","journal-title":"Toxicol. Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.fm.2011.08.016","article-title":"Infection capacities in the orange-pathogen relationship: Compatible (Penicillium digitatum) and incompatible (Penicillium expansum) interactions","volume":"29","author":"Vilanova","year":"2012","journal-title":"Food Microbiol."},{"key":"ref_16","first-page":"741","article-title":"Immersion of \u201cCoscia\u201d pear fruit in water at 55 degrees C for 60 sec controls Penicillium expansum decay and delays ripening during short storage","volume":"75","author":"Dore","year":"2010","journal-title":"Commun. Agric. Appl. Biol. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.fm.2012.09.011","article-title":"Inhibition of Penicillium expansum by an oxidative treatment","volume":"33","author":"Cerioni","year":"2013","journal-title":"Food Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"79","DOI":"10.3389\/fmicb.2012.00079","article-title":"Chemosensitization as a means to augment commercial antifungal agents","volume":"3","author":"Campbell","year":"2012","journal-title":"Front. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1093\/jac\/dkq031","article-title":"Squalamine, an original chemosensitizer to combat antibiotic-resistant gram-negative bacteria","volume":"65","author":"Lavigne","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.ijantimicag.2013.12.009","article-title":"Combination of fluconazole with non-antifungal agents: A promising approach to cope with resistant Candida albicans infections and insight into new antifungal agent discovery","volume":"43","author":"Liu","year":"2014","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1128\/AAC.48.4.1256-1271.2004","article-title":"Chemosensitization of fluconazole resistance in Saccharomyces cerevisiae and pathogenic fungi by a D-octapeptide derivative","volume":"48","author":"Niimi","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1476-0711-10-23","article-title":"Antifungal activity of redox-active benzaldehydes that target cellular antioxidation","volume":"10","author":"Kim","year":"2011","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"870","DOI":"10.2174\/0929867321666131218094848","article-title":"Synergy against fungal pathogens: Working together is better than working alone","volume":"21","author":"Musiol","year":"2014","journal-title":"Curr. Med. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1017\/S0031182013002072","article-title":"Progress and prospects for targeting Hsp90 to treat fungal infections","volume":"141","author":"Veri","year":"2014","journal-title":"Parasitology"},{"key":"ref_25","unstructured":"Clinical and Laboratory Standards Institute (CLSI) (2008). Reference Method for Broth dilution Antifungal Susceptibility Testing of Filamentous Fungi: Approved Standard, Clinical and Laboratory Standards Institute. [2nd ed.]. CLSI document M38-A2."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1094\/PHYTO-98-4-0427","article-title":"Characterization of fludioxonil-resistant and pyrimethanil-resistant phenotypes of Penicillium expansum from apple","volume":"98","author":"Li","year":"2008","journal-title":"Phytopathology"},{"key":"ref_27","unstructured":"Isenberg, H.D. (1992). Clinical Microbiology Procedures Handbook, American Society for Microbiology. [1 ed.]."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1094\/PHYTO-97-11-1491","article-title":"Penicillium digitatum suppresses production of hydrogen peroxide in host tissue during infection of citrus fruit","volume":"97","author":"Macarisin","year":"2007","journal-title":"Phytopathology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.mib.2014.05.001","article-title":"Are mitochondria the Achilles\u2019 heel of the Kingdom Fungi?","volume":"20","author":"Chatre","year":"2014","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7145","DOI":"10.1128\/AEM.69.12.7145-7152.2003","article-title":"Identification and characterization of benzimidazole resistance in Monilinia fructicola from stone fruit orchards in California","volume":"69","author":"Ma","year":"2003","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1023\/A:1006958623733","article-title":"Growth at different temperatures and on fungicide amended media: Two characteristics to distinguish Colletotrichum species pathogenic to rubber","volume":"143","author":"Jayasinghe","year":"1998","journal-title":"Mycopathologia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1111\/j.1365-2958.2004.04244.x","article-title":"Fungicide activity through activation of a fungal signalling pathway","volume":"53","author":"Kojima","year":"2004","journal-title":"Mol. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Odds, F.C. (2003). Synergy, antagonism, and what the chequerboard puts between them. J. Antimicrob. Chemother., 52.","DOI":"10.1093\/jac\/dkg301"},{"key":"ref_34","unstructured":"Kirkman, T.W. Statistics to Use. Available online: http:\/\/www.physics.csbsju.edu\/stats\/."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.intimp.2014.02.019","article-title":"(5-Hydroxy-4-oxo-4H-pyran-2-yl)methyl 6-hydroxynaphthalene-2-carboxylate, a kojic acid derivative, inhibits inflammatory mediator production via the suppression of Syk\/Src and NF-\u03baB activation","volume":"20","author":"Dung","year":"2014","journal-title":"Int. Immunopharmacol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/19\/11\/18448\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:09:14Z","timestamp":1760216954000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/19\/11\/18448"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,12]]},"references-count":35,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2014,11]]}},"alternative-id":["molecules191118448"],"URL":"https:\/\/doi.org\/10.3390\/molecules191118448","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11,12]]}}}