Macelignan inhibits bee pathogenic fungi <i>Ascophaera apis</i> growth through HOG1 pathway

다국어 초록 (Multilingual Abstract)

<P><I>Ascosphaera apis</I> is a bee pathogen that causes bee larvae infection disease, to which treatment is not yet well investigated. The aim of this study was to investigate antifungal susceptibility <I>in vitro</I> against <I>A. apis</I> and to identify a new antifungal agent for this pathogen through minimal inhibitory concentration (MIC) assay and western blot analysis. Macelignan had 1.56 and 3.125 μg/mL MIC against <I>A. apis</I> after 24 and 48 h, respectively, exhibiting the strongest growth inhibition against <I>A. apis</I> among the tested compounds (corosolic acid, dehydrocostus lactone, loganic acid, tracheloside, fangchinoline and emodin-8-O-β-D-glucopyranoside). Furthermore, macelignan showed a narrow-ranged spectrum against various fungal strains without any mammalian cell cytotoxicity. In spite of miconazole having powerful broad-ranged anti-fungal activity including <I>A. apis</I>, it demonstrated strong cytotoxicity. Therefore, even if macelignan alone was effective as an antifungal agent to treat <I>A. apis</I>, combined treatment with miconazole was more useful to overcome toxicity, drug resistance occurrence and cost effectiveness. Finally, HOG1 was revealed as a target molecule of macelignan in the anti-<I>A. apis</I> activity by inhibiting phosphorylation using <I>S. cerevisiae</I> as a model system. Based on our results, macelignan, a food-grade antimicrobial compound, would be an effective antifungal agent against <I>A. apis</I> infection in bees.</P>