Department of Biotechnology and Bioindustry Sciences, College of Biosciences and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
International Center for the Scientific Development of Shrimp Aquaculture, National Cheng Kung University, Tainan 701, Taiwan.
Cell Microbiol. 2018 Aug;20(8):e12849. doi: 10.1111/cmi.12849. Epub 2018 May 9.
An emerging bacterial disease, acute hepatopancreatic necrosis disease (AHPND), is caused by strains of Vibrio parahaemolyticus with an additional AHPND-associated plasmid pVA1 encoding a virulent toxin (Pir ) that damages the shrimp's hepatopancreas. Like other species of Vibrio, these virulent strains initially colonise the shrimp's stomach, but it is not yet understood how the bacteria or toxins are subsequently able to cross the epithelial barrier and reach the hepatopancreas. Here, by using transcriptomics and system biology methods, we investigate AHPND-induced changes in the stomach of AHPND-causing V. parahaemolyticus (5HP)-infected shrimp and identify host molecular mechanisms that might explain how the integrity of the stomach barrier is compromised. We found that the expression of 376 unique genes was differentially regulated by AHPND infection. Gene ontology, protein interaction, and gene-to-gene correlation expression interaction analyses indicated that in addition to the immune system, a number of these genes were involved in cytoskeleton regulation by Rho GTPase. The involvement of Rho pathway regulation during AHPND pathogenesis was further supported by experiments showing that while Rho inhibitor pretreatment delayed the infection, pretreatment with Rho activator enhanced the pathogenicity of 5HP, and both the bacteria and toxin were detected sooner in the hepatopancreas. Further, disruption of the stomach epithelial structure was found in both Rho preactivated shrimp and in 5HP-infected shrimp. Taken together, we interpret our results to mean that Rho signalling helps to mediate AHPND pathogenesis in shrimp.
一种新兴的细菌性疾病，急性肝胰腺坏死病（AHPND），是由携带额外的 AHPND 相关质粒 pVA1 的副溶血弧菌菌株引起的，该质粒编码一种具有毒性的毒素（Pir），可损害虾的肝胰腺。与其他弧菌一样，这些毒力菌株最初定植在虾的胃中，但目前尚不清楚细菌或毒素是如何随后能够穿过上皮屏障并到达肝胰腺的。在这里，我们使用转录组学和系统生物学方法研究了 AHPND 引起的携带 AHPND 的副溶血弧菌（5HP）感染虾胃的变化，并确定了宿主分子机制，这些机制可能解释了胃屏障的完整性是如何受到损害的。我们发现，376 个独特基因的表达因 AHPND 感染而受到差异调节。基因本体、蛋白质相互作用和基因-基因相互表达关系分析表明，除了免疫系统外，这些基因中的许多基因参与了 Rho GTPase 调节的细胞骨架。Rho 途径调节在 AHPND 发病机制中的参与进一步得到了实验的支持，实验表明，虽然 Rho 抑制剂预处理延迟了感染，但 Rho 激活剂预处理增强了 5HP 的致病性，细菌和毒素都更早地在肝胰腺中被检测到。此外，在 Rho 预先激活的虾和 5HP 感染的虾中都发现了胃上皮结构的破坏。综上所述，我们的解释是 Rho 信号有助于介导虾的 AHPND 发病机制。
