嗜水气单胞菌分泌型丝氨酸蛋白酶Ssp1通过抑制合方鲫IL-22/STAT3信号通路破坏肠黏膜屏障的机制研究

嗜水气单胞菌是一种广宿主范围的水产养殖动物病原菌，可引起细菌性败血症，给养殖业造成严重经济损失。肠黏膜屏障对于阻止病原菌入侵宿主至关重要，但嗜水气单胞菌突破肠道黏膜屏障的机制尚不十分清楚。申请人前期初步发现，致病性嗜水气单胞菌的一种分泌型丝氨酸蛋白酶Ssp1（Secreted serine protease 1）能导致合方鲫IL-22表达显著下调，以及造成肠黏膜屏障能力显著降低。为揭示嗜水气单胞菌Ssp1破坏鱼类肠黏膜屏障的机制，本项目拟运用分子生物学等方法，确定合方鲫IL-22对肠黏膜屏障的保护作用，鉴定嗜水气单胞菌Ssp1是一个破坏肠黏膜屏障的毒力因子，进而阐明嗜水气单胞菌Ssp1通过抑制IL-22/STAT3信号通路破坏合方鲫肠黏膜屏障的分子机制。本申请项目研究结果将进一步加深我们对嗜水气单胞菌破坏肠黏膜屏障机制的了解，并为水产养殖生物细菌性疾病的防控提供理论指导。

Aeromonas hydrophila is a wide host range of pathogenic bacteria in aquaculture animals, which can cause bacterial sepsis and serious economic losses to the aquaculture industry. The intestinal mucosal barrier is crucial for preventing pathogens from invading the host, but the mechanism by which A. hydrophila breaks through the intestinal barrier is not yet fully understood. Our preliminary work has initially found that Ssp1, a secreted serine protease of pathogenic A. hydrophila, can significantly reduce the expression of IL-22 and cause a significant decrease in the ability of intestinal barrier in crucian carp (Carassius auratus cuvieri ♀ × Carassius auratus red var. ♂). In order to reveal the mechanism of A. hydrophila Ssp1 destroying intestinal mucosal barrier in fish, this project intends to analyze the protective effect of crucian carp IL-22 on the intestinal mucosal barrier by molecular biology technologies, and identify A. hydrophila Ssp1 as a virulence factor that destroys the intestinal mucosal barrier, then clarify the molecular mechanism of A. hydrophila Ssp1 inhibiting IL-22/STAT3 to destroy the intestinal mucosal barrier of crucian carp. The results of this project will further deepen our understanding of the mechanism of A. hydrophila destroying the intestinal mucosal barrier, and provide theoretical guidance for the prevention and control of bacterial diseases in aquaculture organisms.