Document Detail


Bacterial toxins can inhibit host cell autophagy through cAMP generation.
MedLine Citation:
PMID:  21606683     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Autophagy plays a significant role in innate and adaptive immune responses to microbial infection. Some pathogenic bacteria have developed strategies to evade killing by host autophagy. These include the use of 'camouflage' proteins to block targeting to the autophagy pathway and the use of pore-forming toxins to block autophagosome maturation. However, general inhibition of host autophagy by bacterial pathogens has not been observed to date. Here we demonstrate that bacterial cAMP-elevating toxins from B. anthracis and V. cholera can inhibit host antimicrobial autophagy, including autophagic targeting of S. Typhimurium and latex bead phagosomes. Autophagy inhibition required the cAMP effector protein kinase A. Formation of autophagosomes in response to rapamycin and the endogenous turnover of peroxisomes was also inhibited by cAMP-elevating toxins. These findings demonstrate that cAMP-elevating toxins, representing a large group of bacterial virulence factors, can inhibit host autophagy to suppress immune responses and modulate host cell physiology.
Authors:
Shahab Shahnazari; Anton Namolovan; Jeremy Mogridge; Peter K Kim; John H Brumell
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-01
Journal Detail:
Title:  Autophagy     Volume:  7     ISSN:  1554-8635     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-5-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101265188     Medline TA:  Autophagy     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Cell Biology Program; Hospital for Sick Children; Toronto, ON Canada; Department of Molecular Genetics; University of Toronto; Toronto, ON Canada.
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