Document Detail


Escherichia coli subtilase cytotoxin induces apoptosis regulated by host Bcl-2 family proteins Bax/Bak.
MedLine Citation:
PMID:  20713620     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Subtilase cytotoxin (SubAB) was first isolated from a Shiga toxigenic Escherichia coli (STEC) strain that was responsible for an outbreak of hemolytic-uremic syndrome and is the prototype of a new family of AB(5) cytotoxins. SubAB is a subtilase-like serine protease, and upon uptake by host cells, it is trafficked to the endoplasmic reticulum (ER), where it cleaves the essential ER chaperone BiP (GRP78) with high specificity. Previous work has shown that BiP cleavage by SubAB initiates ER stress-signaling pathways in host cells that eventuate in cell death associated with DNA fragmentation, a hallmark of apoptosis. The present study has investigated the role of the Bcl-2 protein family, which has been shown to regulate ER stress-induced apoptosis in other model systems. Examination of the cytotoxicity of SubAB for wild-type and bax(-/-)/bak(-/-) mouse embryonic fibroblasts and comparison of apoptotic markers in these cells revealed that SubAB cytotoxicity can be predominantly attributed to the activation of apoptotic pathways activated by Bax/Bak. The results of the present study further our understanding of the molecular mechanism whereby SubAB kills eukaryotic cells and contributes to STEC pathogenesis, in addition to consolidating the roles of Bcl-2 family members in the regulation of ER stress-induced apoptosis.
Authors:
Kerrie L May; James C Paton; Adrienne W Paton
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-08-16
Journal Detail:
Title:  Infection and immunity     Volume:  78     ISSN:  1098-5522     ISO Abbreviation:  Infect. Immun.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-19     Completed Date:  2010-11-12     Revised Date:  2011-07-28    
Medline Journal Info:
Nlm Unique ID:  0246127     Medline TA:  Infect Immun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4691-6     Citation Subset:  IM    
Affiliation:
Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA, Australia.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis*
Cercopithecus aethiops
DNA Fragmentation
Endoplasmic Reticulum / physiology
Escherichia coli Proteins / toxicity*
Fibroblasts
Gene Expression Regulation*
Mice
Shiga-Toxigenic Escherichia coli / pathogenicity*
Subtilisins / toxicity*
Vero Cells
bcl-2 Homologous Antagonist-Killer Protein / metabolism*
bcl-2-Associated X Protein / metabolism*
Grant Support
ID/Acronym/Agency:
R01 AI-068715/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Escherichia coli Proteins; 0/bcl-2 Homologous Antagonist-Killer Protein; 0/bcl-2-Associated X Protein; EC 3.4.21.-/Subtilisins; EC 3.4.21.-/subtilase cytotoxin, E coli
Comments/Corrections

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