The bacterial effectors EspG and EspG2 induce a destructive calpain activity that is kept in check by the

Paul Dean1, Sabrina Mühlen, Sabine Quitard

  • 1Institute for Cell and Molecular Biosciences, Medical School, University of Newcastle, Newcastle-Upon-Tyne NE2 4HH, UK.

Cellular Microbiology
|March 30, 2010
PubMed

Insights

Absence of the enteropathogenic E. coli (EPEC) effector Tir triggers EspG/EspG2 to activate calpain, causing intestinal epithelial destruction. Tir is crucial for maintaining epithelial integrity by regulating these destructive effector activities.

Area of Science:

  • Microbiology and Immunology
  • Cell Biology
  • Pathogen-Host Interactions

Background:

  • Bacterial pathogens utilize effector proteins to manipulate host cells.
  • Cooperation between bacterial effectors is critical for subverting host processes.
  • Enteropathogenic E. coli (EPEC) employs various effectors during infection.

Purpose of the Study:

  • To investigate the role of EPEC effector balance in infection outcomes.
  • To elucidate the mechanism by which EPEC disrupts intestinal epithelial integrity.
  • To determine the specific functions of EPEC effectors Tir, EspG, and EspG2 in host cell manipulation.

Main Methods:

  • Analysis of EPEC infection models lacking specific effector proteins.
  • Investigation of host cell detachment and epithelial destruction.
  • Assays to detect the activation of host cysteine protease calpain by EPEC effectors.

Main Results:

  • Absence of the EPEC effector Tir leads to potent destruction of polarized intestinal epithelia.
  • EPEC effectors EspG and EspG2 activate the host protease calpain in a Tir-dependent manner.
  • Calpain activation significantly increases in the absence of Tir, causing rapid host cell loss and necrosis.

Conclusions:

  • EPEC effector Tir is essential for maintaining intestinal epithelial integrity during infection.
  • Tir regulates the destructive activity of EspG and EspG2, preventing excessive host cell damage.
  • EspG and EspG2 possess a novel function in activating calpain, contributing to pathogen-induced cytopathology.

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