Related Experiment Video

Updated: May 20, 2025

High-throughput Assay to Phenotype Salmonella enterica Typhimurium Association, Invasion, and Replication in Macrophages
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High-throughput Assay to Phenotype Salmonella enterica Typhimurium Association, Invasion, and Replication in Macrophages

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The ER-phagy receptor FAM134B is targeted by Salmonella Typhimurium to promote infection

Damián Gatica1, Reham M Alsaadi1, Rayan El Hamra2

  • 1Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.

Nature Communications
|March 26, 2025
PubMed

Insights

Salmonella Typhimurium evades cellular defenses by inhibiting ER-phagy, a process crucial for clearing damaged cell components. This bacterial strategy, mediated by targeting the FAM134B receptor, enhances Salmonella survival and causes severe intestinal damage.

Area of Science:

  • Cellular Biology
  • Immunology
  • Microbiology

Background:

  • Macroautophagy/autophagy is a vital cellular recycling process targeting damaged organelles and pathogens.
  • Endoplasmic reticulum selective autophagy (ER-phagy) maintains ER homeostasis and responds to infection.
  • Mechanisms by which bacteria like Salmonella evade ER-phagy are not well understood.

Purpose of the Study:

  • To investigate the interplay between ER-phagy and Salmonella Typhimurium infection.
  • To elucidate the mechanisms Salmonella employs to escape ER-phagy-mediated degradation.
  • To determine the role of the ER-phagy receptor FAM134B in innate immunity against Salmonella.

Main Methods:

  • Investigated Salmonella's effect on ER-phagy and the FAM134B receptor.
  • Utilized FAM134B knockout models and assessed Salmonella burden and host damage.
  • Analyzed the role of the bacterial effector SopF in modulating ER-phagy.

Main Results:

  • Salmonella Typhimurium inhibits ER-phagy by preventing FAM134B oligomerization, crucial for ER-phagy.
  • FAM134B knockout increased intracellular Salmonella burden, while FAM134B activation reduced it.
  • The bacterial effector SopF targets FAM134B to inhibit ER-phagy, enhancing Salmonella survival.
  • FAM134B knockout mice showed severe intestinal damage and higher bacterial loads upon Salmonella infection.

Conclusions:

  • Salmonella actively inhibits ER-phagy by targeting FAM134B to promote intracellular survival.
  • FAM134B plays a critical role in innate immunity against Salmonella infection.
  • Understanding Salmonella's ER-phagy evasion provides insights into host-pathogen interactions.

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