Abstract

The fungal antioxidant system is one of the targets of the redox-active polyene antifungal drugs, including amphotericin B (AMB), nystatin (NYS), and natamycin (NAT). Besides medical applications, NAT has been used in industry for preserving foods and crops. In this study, we investigated two parameters (pH and food ingredients) affecting NAT efficacy. In the human pathogen, Aspergillus fumigatus, NAT (2 to 16 μg mL−1) exerted higher activity at pH 5.6 than at pH 3.5 on a defined medium. In contrast, NAT exhibited higher activity at pH 3.5 than at pH 5.6 against foodborne fungal contaminants, Aspergillus flavus, Aspergillus parasiticus, and Penicillium expansum, with P. expansum being the most sensitive. In commercial food matrices (10 organic fruit juices), food ingredients differentially affected NAT antifungal efficacy. Noteworthily, NAT overcame tolerance of the A. fumigatus signaling mutants to the fungicide fludioxonil and exerted antifungal synergism with the secondary metabolite, kojic acid (KA). Altogether, NAT exhibited better antifungal activity at acidic pH against foodborne fungi; however, the ingredients from commercial food matrices presented greater impact on NAT efficacy compared to pH values. Comprehensive determination of parameters affecting NAT efficacy and improved food formulation will promote sustainable food/crop production, food safety, and public health.

Highlights

  • One Health recognizes that people, animals, plants, and their shared environment are highly interconnected

  • SakA and MpkC are orthologous proteins to the high osmolality glycerol (HOG) mitogen-activated protein kinases (MAPKs) protein (Hog1p) of the model yeast Saccharomyces cerevisiae, which is involved in oxidative stress signaling/defense [38]

  • We investigated parameters that affect the antifungal efficacy of NAT in potato dextrose agar (PDA) and commercial food matrices (10 fruit juices)

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Summary

Introduction

One Health recognizes that people, animals, plants, and their shared environment are highly interconnected. Cross-resistance of fungi to azole and polyene drugs has become a prominent public and environmental health issue [7]. Azoles, such as voriconazole (VRZ), itraconazole (ITR), or posaconazole (POS), are broadly used for treating human fungal pathogens. The primary mechanism of antifungal action of azoles is to inhibit the lanosterol 14-α sterol demethylase (CYP51 of the cytochrome P450 monooxygenase (CYP) superfamily) involved in fungal ergosterol biosynthesis [8,9] Polyene drugs, such as amphotericin B (AMB), nystatin (NYS), and natamycin (NAT) ( known as pimaricin), contain conjugated double bonds in the structure, providing high affinity to ergosterol moiety of membranes in most fungal species [10]

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