Deoxynivalenol (DON) is a vital virulence factor of Fusarium graminearum, which causes Fusarium head blight (FHB). We recently found that validamycin A (VMA), an aminoglycoside antibiotic, can be used to control FHB and inhibit DON contamination, but its molecular mechanism is still unclear. In this study, we found that both neutral and acid trehalase (FgNTH and FgATH) are the targets of VMA in F. graminearum, and the deficiency of FgNTH and FgATH reduces the sensitivity to VMA by 2.12- and 1.79-fold, respectively, indicating that FgNTH is the main target of VMA. We found FgNTH is responsible for vegetative growth, FgATH is critical to sexual reproduction, and both of them play an important role in conidiation and virulence in F. graminearum. We found that FgNTH resided in the cytoplasm, affected the localization of FgATH, and positively regulated DON biosynthesis; however, FgATH resided in vacuole and negatively regulated DON biosynthesis. FgNTH interacted with FgPK (pyruvate kinase), a key enzyme in glycolysis, and the interaction was reduced by VMA; the deficiency of FgNTH affected the localization of FgPK under DON induction condition. Strains with a deficiency of FgNTH were more sensitive to demethylation inhibitor (DMI) fungicides. FgNTH regulated the expression level of FgCYP51A and FgCYP51B by interacting with FgCYP51B. Taken together, VMA inhibits DON biosynthesis by targeting FgNTH and reducing the interaction between FgNTH and FgPK, and synergizes with DMI fungicides against F. graminearum by decreasing FgCYP51A and FgCYP51B expression.

中文翻译：

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有效霉素A抑制DON生物合成并与DMI杀菌剂协同对抗禾谷镰刀菌的机制

脱氧雪腐镰刀菌烯醇 (DON) 是禾谷镰刀菌的重要毒力因子，可导致镰刀菌枯萎病 (FHB)。我们最近发现氨基糖苷类抗生素validamycin A (VMA)可用于控制FHB和抑制DON污染，但其分子机制尚不清楚。在这项研究中，我们发现中性和酸性海藻糖酶（FgNTH 和 FgATH）都是F中 VMA 的目标。 graminearum以及 FgNTH 和 FgATH 的缺乏使对 VMA 的敏感性分别降低了 2.12 倍和 1.79 倍，表明 FgNTH 是 VMA 的主要靶点。我们发现 FgNTH 负责营养生长，FgATH 对有性繁殖至关重要，两者都在F 的分生孢子和毒力中发挥重要作用。 菌。我们发现FgNTH存在于细胞质中，影响FgATH的定位，并正调控DON的生物合成；然而，FgATH 存在于液泡中并负调控 DON 的生物合成。FgNTH与糖酵解的关键酶FgPK（丙酮酸激酶）相互作用，VMA降低了相互作用；FgNTH的缺乏影响了DON诱导条件下FgPK的定位。缺乏 FgNTH 的菌株对去甲基化抑制剂 (DMI) 杀菌剂更敏感。FgNTH通过与 FgCYP51B 相互作用调节FgCYP51A和FgCYP51B的表达水平。总之，VMA 通过靶向 FgNTH 并减少 FgNTH 和 FgPK 之间的相互作用来抑制 DON 生物合成，并与 DMI 杀菌剂协同作用˚F。graminearum通过降低FgCYP51A和FgCYP51B 的表达。