Synergistic anti-oomycete effect of melatonin with a biofungicide against oomycetic black shank disease

Human health, food safety, and agriculture have been threatened by oomycetic diseases caused by notorious pathogenic oomycetes. Chemical oomyceticides are the main approaches in control of pathogenic oomycetes. However, the overused chemical oomyceticides have resulted in serious environmental pollution and drug resistance. The eco-friendly bio-oomyceticides are required for sustainable development through screening synergistic drug combinations. In this study, Phytophthora nicotianae (P. nicotianae), as one of the most destructive oomycetic diseases in agriculture, was used as a model system to screen the novel bio-oomyceticides based on drug combination. The results showed that treatment of melatonin or ethylicin (IUPAC Name: 1-ethylsulfonylsulfanylethane) alone displayed similar phenotypes such as the inhibition of the hyphal growth, reduction of the cell viability, and suppression of the virulence of P. nicotianae. Importantly, melatonin and ethylicin shared the same targets of interfering with the amino acid metabolism, overexpressing apoptosis-inducing factor, and dysregulating the virulence-related genes. Furthermore, strong synergism against P. nicotianae was induced by combining melatonin with ethylicin. Under treatment of the combination of melatonin and ethylicin, the expression of genes associated with amino acid, the apoptosis-inducing factor, and the virulence-related genes was much more significantly dysregulated than that of single drug treatment. Thus, the tobacco black shank caused by P. nicotianae can be successfully controlled using the combination of melatonin and ethylicin. These observations suggest that the synergistic effect based on the combination of melatonin and ethylicin is an eco-friendly alternative for the control of the destructive oomycetic diseases.