|Kim, Jong Heon|
|Chan, Kathleen - Kathy|
|Cheng, Luisa Wai Wai|
|LAND, KIRKWOOD - University Of The Pacific|
|Chang, Perng Kuang|
Submitted to: Foods
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/27/2021
Publication Date: 9/2/2021
Citation: Kim, J., Tam, C.C., Chan, K.L., Cheng, L.W., Land, K.M., Friedman, M., Chang, P. 2021. Antifungal efficacy of redox-active natamycin against some foodborne fungi—comparison with aspergillus fumigatus. Foods. 10(9):2073. https://doi.org/10.3390/foods10092073.
Interpretive Summary: Control of fungal contaminations or diseases is increasingly problematic since the number of effective antifungal drugs available for antifungal therapy is often very limited. Also, contamination of food by fungi harmful to human health is a recurring food safety issue. While outbreaks in commodity-specific food sources by hepato-carcinogenic mycotoxins trigger non-infectious ailment, food contamination by infectious fungi could directly affect the health and safety of the public. Natamycin (NAT), amphotericin B and nystatin belong to polyene drugs which possess a broad spectrum of antifungal activity against filamentous and yeast-form fungi. Among the polyene drugs, NAT has also been used for control of fungi infecting/contaminating crops (mushroom, tomato, strawberry, etc.) or processed foods (table olives, fruit juices, cheeses, yogurt, wines, etc.). In this study, we determined the potent redox-activity of NAT and differential antifungal activity of NAT between the human pathogen A. fumigatus and mycotoxigenic/foodborne fungal pathogens (A. flavus, A. parasiticus, P. expansum). NAT showed promise for preserving foods at acidic pHs against foodborne fungi; one of the proposed antifungal mechanisms is targeting the fungal antioxidant system.
Technical Abstract: The fungal antioxidant system is one of the targets of polyene antifungal drugs, such as amphotericin B (AMB) and nystatin (NYS). The polyenes are redox-active molecules, which control broad-spectrum yeast and filamentous fungal pathogens, including Aspergillus spp., Fusarium spp., Candida spp., etc. The other clinical polyene drug natamycin (NAT; a.k.a. pimaricin) has also been used in food/agricultural industries for treating fungi contaminating foods or infecting crops. Since invasive fungal infections (and mycotoxin uptake) in humans are also acquired from contaminated foods, there have been discussions on whether the broad utility of NAT can trigger the emergence of fungal pathogens cross-resistant to other polyenes or antimycotic drugs. We investigated the parameters affecting NAT efficacy for better prevention of fungal infection or contamination in foods. We found the potent redox-activity of NAT, where the sakA' and mpkC', two oxidative signaling mutants lacking the mitogen-activated protein kinase (MAPK) genes of Aspergillus fumigatus, exhibited increased sensitivity to NAT (as well as to AMB and NYS; order of redox activity, high to low: AMB > NAT > NYS) when compared to the wild type control. In A. fumigatus, NAT exerted much higher antifungal activity at pH 5.6 than at pH 3.5 on the potato dextrose medium (NAT: 2, 4, 8, 16 'g mL-1). We investigated NAT antifungal efficacy further in foodborne fungi, namely, mycotoxin-producing (Aspergillus flavus, Aspergillus parasiticus, Penicillium expansum) and heat-resistant (Neosartorya fischeri) strains contaminating foods or crops. Interestingly, NAT exhibited higher antimycotic activity at pH 3.5 than at pH 5.6 towards foodborne fungi, which was contrary to the A. fumigatus results. P. expansum was the most sensitive fungus to NAT. In commercial food matrices (ten fruit juices; pH range: 3.08 to 3.99), food ingredients differentially affected NAT efficacies on test fungi. Remarkably, NAT overcame the tolerance of A. fumigatus MAPK mutants to the commercial fungicide fludioxonil. While NAT and kojic acid (KA) were synergistic, their antifungal efficacy was not comparable to that of KA combined with AMB. Altogether, NAT showed promise for preserving foods at acidic pHs against foodborne fungi; one of the proposed antifungal mechanisms is targeting the fungal antioxidant system. Future in-depth investigation will further the safe usage of NAT, thus promoting the food safety and security and One Health.