Analysis on pathogenic mechanism of fish pathogen Edwardsiella tarda

(1)迟缓爱德华氏菌在小鼠巨噬细胞中的细胞内复制依赖于III型分泌系统迟缓爱德华氏菌是一种具有广泛宿主范围的病原体，可感染动物和人类。对吞噬细胞杀伤的抗性可能与该细菌的致病性有关。结果表明，E.小鼠巨噬细胞中的迟发依赖于III型分泌系统，并通过上调抗凋亡NF-κ B靶基因诱导抗凋亡作用。野生型菌株在巨噬细胞的吞噬体膜内复制;而III型突变体则不复制。(2)微阵列分析微阵列分析显示，与感染III型突变体的巨噬细胞相比，感染野生型菌株的巨噬细胞中NF-κ B靶基因（例如促炎细胞因子和抗凋亡基因）的mRNA表达水平上调。抗凋亡NF-kappaB靶基因的上调是导致细胞凋亡的原因。 ...更多信息 抗凋亡活性。（3）NF-κ B活化对人上皮细胞中迟缓爱德华氏菌细胞内生长的III型分泌系统依赖性抑制我们接下来表明，TTSS也是人上皮细胞（Hep-2）中细菌细胞内生长所需的。然而，与先前的小鼠巨噬细胞的微阵列分析不同，在感染的Hep-2细胞中未检测到NF-κ B靶基因的mRNA表达水平的上调。野生型E tarda，而不是其TTSS突变体，实际上抑制了肿瘤坏死因子α依赖的NF-κ B激活在NF-κ B报告基因测定。这些结果表明，TTSS依赖的抑制NF-κ B活化的Hep-2细胞感染E。这些结果表明，针对该菌III型分泌系统的药物或疫苗可能有助于减少E. tarda造成的工业损失。养殖鱼类如真鲷和日本比目鱼的迟发性感染。少

(1) Intracellular replication of Edwardsiella tarda in murine macrophage is dependent on the type III secretion systemEdwardsiella tarda is a pathogen with a broad host range that infects both animals and humans. Resistance to phagocytic killing may be involved in the pathogenicity of this bacterium. We showed that intracellular replication of E. tarda in murine macrophages is dependent on the type III secretion system and induces an anti-apoptotic effect by up-regulating anti-apoptotic NF-kappaB target genes. The wild-type strain replicates within the phagosomal membrane of macrophages ; whereas the type III mutant does not.(2) Microarray analysisMicroarray analysis shows the mRNA expression level of NF-kappaB target genes (e.g. pro-inflammatory cytokines and anti-apoptotic genes) in macrophages infected with the wild-type strain were up-regulated compared to macrophages infected with the type III mutant. Up-regulation of anti-apoptotic NF-kappaB target genes is responsible for the an … More ti-apoptotic activity of E. tarda and is required for intracellular replication in murine macrophages(3) The type III secretion system-dependent repression of NF-kappaB activation to the intracellular growth of Edwardsiella tarda in human epithelial cellsWe next showed that the TTSS is also needed for intracellular growth of the bacterium in human epithelial cells (Hep-2). However, different from the previous microarray analyses on murine macrophages, upregulation of the mRNA expression level of NF-kappaB target genes was not detected in the infected Hep-2 cells. The wild-type E tarda, but not its TTSS mutant, actually repressed the tumor necrosis factor alpha-dependent NF-kappaB activation in an NF-kappaB reporter gene assay. These results suggest TTSS-dependent repression of the NF-kappaB activation in Hep-2 cells infected with E. tarda.Taken together, these results suggest that drug or vaccine specifically targeting the type III secretion system of this bacterium may contribute to decreasing the industrial loss caused by E. tarda infection to cultured fish such as red sea bream and Japanese flounder. Less