Michael G. DeGroote Institute for Infectious Disease Research and the Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
PLoS Pathog. 2012;8(6):e1002773. doi: 10.1371/journal.ppat.1002773. Epub 2012 Jun 28.
Bacterial pathogens often manipulate host immune pathways to establish acute and chronic infection. Many Gram-negative bacteria do this by secreting effector proteins through a type III secretion system that alter the host response to the pathogen. In this study, we determined that the phage-encoded GogB effector protein in Salmonella targets the host SCF E3 type ubiquitin ligase through an interaction with Skp1 and the human F-box only 22 (FBXO22) protein. Domain mapping and functional knockdown studies indicated that GogB-containing bacteria inhibited IκB degradation and NFκB activation in macrophages, which required Skp1 and a eukaryotic-like F-box motif in the C-terminal domain of GogB. GogB-deficient Salmonella were unable to limit NFκB activation, which lead to increased proinflammatory responses in infected mice accompanied by extensive tissue damage and enhanced colonization in the gut during long-term chronic infections. We conclude that GogB is an anti-inflammatory effector that helps regulate inflammation-enhanced colonization by limiting tissue damage during infection.
细菌病原体经常操纵宿主免疫途径来建立急性和慢性感染。许多革兰氏阴性菌通过一种 III 型分泌系统将效应蛋白分泌到宿主中，从而改变宿主对病原体的反应。在这项研究中，我们确定了沙门氏菌中噬菌体编码的 GogB 效应蛋白通过与 Skp1 和人类 F-box 仅 22（FBXO22）蛋白相互作用来靶向宿主 SCF E3 型泛素连接酶。结构域映射和功能敲低研究表明，含有 GogB 的细菌抑制了巨噬细胞中 IκB 的降解和 NFκB 的激活，这需要 Skp1 和 GogB C 端结构域中的真核样 F-box基序。GogB 缺陷型沙门氏菌无法限制 NFκB 的激活，这导致感染小鼠中的促炎反应增加，伴有广泛的组织损伤，并在长期慢性感染期间增强肠道定植。我们得出结论，GogB 是一种抗炎效应物，通过在感染期间限制组织损伤来帮助调节炎症增强的定植。
