The ER-phagy receptor FAM134B is targeted by Salmonella Typhimurium to promote infection
crossref(2024)
Abstract
Macroautophagy/autophagy is a key catabolic-recycling pathway that can selectively target damaged organelles or invading pathogens for degradation. The selective autophagic degradation of the endoplasmic reticulum (hereafter referred to as ER-phagy) is a homeostatic mechanism, controlling ER size, the removal of misfolded protein aggregates, and organelle damage. ER-phagy is also stimulated by pathogen infection. However, the link between ER-phagy and bacterial infection remains poorly understood, as are the mechanisms evolved by pathogens to escape the effects of ER-phagy. Here, we show that Salmonella enterica serovar Typhimurium inhibits ER-phagy by targeting the ER-phagy receptor FAM134B, leading to a pronounced increase in Salmonella viability after invasion. Salmonella prevents FAM134B oligomerization, which is required for efficient ER-phagy. FAM134B knock-out raises intracellular Salmonella number, while FAM134B activation reduces Salmonella burden. Additionally, we found that Salmonella targets FAM134B through the bacterial effector SopF to enhance intracellular survival through ER-phagy inhibition. Furthermore, FAM134B knock-out mice infected with Salmonella presented severe intestinal damage and increased bacterial burden. These results provide new mechanistic insight into the interplay between ER-phagy and bacterial infection, highlighting a key role for FAM134B in innate immunity.
### Competing Interest Statement
The authors have declared no competing interest.
* Atg
: autophagy-related
WT
: wild-type
KO
: knock-out
GFP
: Green Fluorescent Protein
RFP
: Red Fluorescent Protein
ss
: signal sequence
BAFA1
: Bafilomycin A1
CFU
: Colony-Forming Unit
LIR
: LC3-interacting region
NAD+
: nicotinamide adenine dinucleotide
SCV
: Salmonella containing vesicles
H&E
: hematoxylin and eosin
BMDM
: Bone Marrow Derived Macrophages
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