A. hydrophila is an important pathogen that mainly harms aquatic animals and has exhibited resistance to a variety of antibiotics. Here, to seek an effective alternative for antibiotics, the effects of umbelliferone (UM) at sub-MICs on A. hydrophila virulence factors and the quorum-sensing system were studied. Subsequently, RNA sequencing was employed to explore the potential mechanisms for the antivirulence activity of umbelliferone. Meanwhile, the protective effect of umbelliferone on grass carp infected with A. hydrophila was studied in vivo. Our results indicated that umbelliferone could significantly inhibit A. hydrophila virulence such as hemolysis, biofilm formation, swimming and swarming motility, and their quorum-sensing signals AHL and AI-2. Transcriptomic analysis showed that umbelliferone downregulated expression levels of genes related to exotoxin, the secretory system (T2SS and T6SS), iron uptake, etc. Animal studies demonstrated that umbelliferone could significantly improve the survival of grass carps infected with A. hydrophila, reduce the bacterial load in the various tissues, and ameliorate cardiac, splenic, and hepatopancreas injury. Collectively, umbelliferone can reduce the pathogenicity of A. hydrophila and is a potential drug for treating A. hydrophila infection.

中文翻译：

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伞形酮的抗毒活性及其对嗜水草鱼感染的保护作用

A. hydrophila是一种重要的病原体，主要危害水生动物，并对多种抗生素表现出耐药性。在这里，为了寻找一种有效的抗生素替代品，研究了亚 MIC 下的伞形酮 (UM) 对A. hydrophila毒力因子和群体感应系统的影响。随后，利用RNA测序来探索伞形酮抗病毒活性的潜在机制。同时，在体内研究了伞形酮对感染A.hydrophila草鱼的保护作用。我们的结果表明，伞形酮可以显着抑制A.hydrophila毒力，如溶血、生物膜形成、游泳和集群运动，以及它们的群体感应信号 AHL 和 AI-2。转录组学分析表明，伞形花酮下调外毒素、分泌系统（T2SS和T6SS）、铁摄取等相关基因的表达水平。动物研究表明，伞形花酮能显着提高草鱼感染A.hydrophila的存活率，减少细菌减轻各种组织的负荷，改善心脏、脾脏和肝胰腺的损伤。总而言之，伞形酮可以降低 A.hydrophila 的致病性，是治疗A.hydrophila感染的潜在药物。