Shigella flexneri type III secreted effector OspF reveals new crosstalks of proinflammatory signaling pathways during bacterial infection

Cell Signal. 2011 Jul;23(7):1188-96. doi: 10.1016/j.cellsig.2011.03.006. Epub 2011 Mar 21.


Shigella flexneri type III secreted effector OspF harbors a phosphothreonine lyase activity that irreversibly dephosphorylates MAP kinases (MAPKs) p38 and ERK in infected epithelial cells and thereby, dampens innate immunity. Whereas this activity has been well characterized, the impact of OspF on other host signaling pathways that control inflammation was unknown. Here we report that OspF potentiates the activation of the MAPK JNK and the transcription factor NF-κB during S. flexneri infection. This unexpected effect of OspF was dependent on the phosphothreonine lyase activity of OspF on p38, and resulted from the disruption of a negative feedback loop regulation between p38 and TGF-beta activated kinase 1 (TAK1), mediated via the phosphorylation of TAK1-binding protein 1. Interestingly, potentiated JNK activation was not associated with enhanced c-Jun signaling as OspF also inhibits c-Jun expression at the transcriptional level. Altogether, our data reveal the impact of OspF on the activation of NF-κB, JNK and c-Jun, and demonstrate the existence of a negative feedback loop regulation between p38 and TAK1 during S. flexneri infection. Furthermore, this study validates the use of bacterial effectors as molecular tools to identify the crosstalks that connect important host signaling pathways induced upon bacterial infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / metabolism*
  • Cell Line
  • Dysentery, Bacillary / immunology
  • Dysentery, Bacillary / metabolism*
  • Enzyme Activation
  • Feedback, Physiological
  • Humans
  • Inflammation / metabolism
  • Inflammation Mediators / metabolism*
  • JNK Mitogen-Activated Protein Kinases / genetics
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Mice
  • Phosphorylases / metabolism
  • Phosphorylation
  • Recombinant Proteins / metabolism*
  • Shigella flexneri*
  • Signal Transduction
  • Transcription Factor RelA / metabolism
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Bacterial Proteins
  • Inflammation Mediators
  • Recombinant Proteins
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • Phosphorylases
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases