Document Detail

Dissemination of invasive Salmonella via bacterial-induced extrusion of mucosal epithelia.
MedLine Citation:
PMID:  20876119     Owner:  NLM     Status:  MEDLINE    
Salmonella enterica is an intracellular bacterial pathogen that resides and proliferates within a membrane-bound vacuole in epithelial cells of the gut and gallbladder. Although essential to disease, how Salmonella escapes from its intracellular niche and spreads to secondary cells within the same host, or to a new host, is not known. Here, we demonstrate that a subpopulation of Salmonella hyperreplicating in the cytosol of epithelial cells serves as a reservoir for dissemination. These bacteria are transcriptionally distinct from intravacuolar Salmonella. They are induced for the invasion-associated type III secretion system and possess flagella; hence, they are primed for invasion. Epithelial cells laden with these cytosolic bacteria are extruded out of the monolayer, releasing invasion-primed and -competent Salmonella into the lumen. This extrusion mechanism is morphologically similar to the process of cell shedding required for turnover of the intestinal epithelium. In contrast to the homeostatic mechanism, however, bacterial-induced extrusion is accompanied by an inflammatory cell death characterized by caspase-1 activation and the apical release of IL-18, an important cytokine regulator of gut inflammation. Although epithelial extrusion is obviously beneficial to Salmonella for completion of its life cycle, it also provides a mechanistic explanation for the mucosal inflammation that is triggered during Salmonella infection of the gastrointestinal and biliary tracts.
Leigh A Knodler; Bruce A Vallance; Jean Celli; Seth Winfree; Bryan Hansen; Marinieve Montero; Olivia Steele-Mortimer
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't     Date:  2010-09-27
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  107     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-13     Completed Date:  2010-11-22     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17733-8     Citation Subset:  IM    
Laboratory of Intracellular Parasites and Research Technologies Branch, Microscopy Unit, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
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MeSH Terms
Caspase 1 / metabolism
Cell Death / physiology
Cell Line, Tumor
Cytoplasm / microbiology*
Fluorescent Antibody Technique
Gastric Mucosa / metabolism,  microbiology*,  physiology
Interleukin-18 / metabolism
Salmonella Infections / transmission*
Salmonella enterica*
Grant Support
//Canadian Institutes of Health Research
Reg. No./Substance:
0/Interleukin-18; EC 1
Comment In:
Nat Rev Microbiol. 2010 Dec;8(12):839   [PMID:  21125702 ]

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