File:Unfolded protein response to bacterial pore-forming toxins.png
Unfolded_protein_response_to_bacterial_pore-forming_toxins.png (600 × 363 pixels, file size: 181 KB, MIME type: image/png)
Schematic illustrating relationship between p38 MAPK, ire-1-xbp-1, and Pore-forming toxins (PFTs) defense pathways
Pore-forming toxins (PFTs) at the cell surface of epithelial cells activate p38 MAPK that activates IRE-1 that induces splicing of xbp-1, which then turns on defense against PFTs. Residual activation of xbp-1 targets in the absence of the p38 MAPK pathway suggests there might be p38-independent activation of the ire-1-xbp-1 pathway in response to PFT as well (not shown). Independent of IRE-1 activation, p38 MAPK can also activate TTM-2 and other PFT defenses. Tunicamycin, which causes the accumulation of unfolded proteins in the ER, activates IRE-1 via a mechanism independent of the PFT and p38 MAPK.
Pore-forming toxins (PFTs) are the single most prevalent protein virulence factor made by disease-causing bacteria and are important for the virulence of many important human pathogens including Staphylococcus aureus, Streptococcus pyogenes, Clostridium perfringens, and Aeromonas hydrophilia ,. Crystal (Cry) toxins produced by the invertebrate pathogen Bacillus thuringiensis (Bt) are a large family of PFTs that target the intestinal cells of insects and nematodes.
The unfolded protein response (UPR) of the endoplasmic reticulum (ER) is a fundamental stress response used by eukaryotic cells to match protein synthesis demand to its capability to fold proteins within the ER to maintain cellular homeostasis
Figure 6. Journal.ppat.1000176.g006.png
Citation: Bischof LJ, Kao C-Y, Los FCO, Gonzalez MR, Shen Z, et al. (2008) Activation of the Unfolded Protein Response Is Required for Defenses against Bacterial Pore-Forming Toxin In Vivo. PLoS Pathog 4(10): e1000176. doi:10.1371/journal.ppat.1000176
Editor: Frederick M. Ausubel, Massachusetts General Hospital, United States of America
Received: June 17, 2008; Accepted: September 15, 2008; Published: October 10, 2008
Copyright: © 2008 Bischof et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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|current||07:56, 10 May 2011||600 × 363 (181 KB)||S8600021||==Schematic illustrating relationship between p38 MAPK, ire-1-xbp-1, and Pore-forming toxins (PFTs) defense pathways== Pore-forming toxins (PFTs) at the cell surface of epithelial cells activate p38 MAPK that activates IRE-1 that induces splicing of xbp-|