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Live-Cell Forward Genetic Approach to Identify and Isolate Developmental Mutants in Chlamydia trachomatis
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Chlamydia trachomatis plasmid-encoded protein pORF5 activates unfolded protein response to induce autophagy via

Yating Wen1, Fangzhen Luo1, Yuqi Zhao1

  • 1Institute of Pathogenic Biology, Hengyang Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, PR China.

Biochemical and Biophysical Research Communications
|May 25, 2020
PubMed

Insights

Chlamydia trachomatis protein pORF5 activates the unfolded protein response (UPR) and induces autophagy. UPR activation by pORF5 is essential for autophagy, mediated through the MAPK/ERK signaling pathway, aiding host cell homeostasis.

Area of Science:

  • Cellular microbiology
  • Molecular biology
  • Host-pathogen interactions

Background:

  • Chlamydia trachomatis (C. trachomatis) is an obligate intracellular bacterium requiring host cell nutrients.
  • C. trachomatis infection induces endoplasmic reticulum (ER) stress.
  • The unfolded protein response (UPR) is activated by chlamydial effectors to aid host recovery.

Purpose of the Study:

  • To investigate the role of C. trachomatis secreted plasmid-encoded protein pORF5.
  • To explore the connection between pORF5, UPR, and autophagy induction.

Main Methods:

  • Activation of UPR branches (PERK, IRE1, ATF6) by pORF5.
  • Assessment of pORF5-induced autophagy using UPR inhibitors (GSK2606414, 4μ8C).
  • Evaluation of MAPK/ERK signaling pathway involvement using PD98059.

Main Results:

  • pORF5 activated all three UPR branches.
  • UPR inhibitors repressed pORF5-induced autophagy, but autophagy inhibition did not affect pORF5-induced UPR.
  • MAPK/ERK inhibition partially suppressed pORF5-induced autophagy, with minimal impact on UPR.

Conclusions:

  • pORF5 activates UPR, which in turn induces autophagy.
  • The MAPK/ERK signaling pathway mediates pORF5-induced autophagy via UPR.
  • These findings offer insights into host cellular homeostasis during C. trachomatis infection.
Keywords:
AutophagyChlamydia trachomatisMAPK/ERKUnfolded protein response

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