Document Detail


Analysis of interactions of Salmonella type three secretion mutants with 3-D intestinal epithelial cells.
MedLine Citation:
PMID:  21206750     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The prevailing paradigm of Salmonella enteropathogenesis based on monolayers asserts that Salmonella pathogenicity island-1 Type Three Secretion System (SPI-1 T3SS) is required for bacterial invasion into intestinal epithelium. However, little is known about the role of SPI-1 in mediating gastrointestinal disease in humans. Recently, SPI-1 deficient nontyphoidal Salmonella strains were isolated from infected humans and animals, indicating that SPI-1 is not required to cause enteropathogenesis and demonstrating the need for more in vivo-like models. Here, we utilized a previously characterized 3-D organotypic model of human intestinal epithelium to elucidate the role of all characterized Salmonella enterica T3SSs. Similar to in vivo reports, the Salmonella SPI-1 T3SS was not required to invade 3-D intestinal cells. Additionally, Salmonella strains carrying single (SPI-1 or SPI-2), double (SPI-1/2) and complete T3SS knockout (SPI-1/SPI-2: flhDC) also invaded 3-D intestinal cells to wildtype levels. Invasion of wildtype and TTSS mutants was a Salmonella active process, whereas non-invasive bacterial strains, bacterial size beads, and heat-killed Salmonella did not invade 3-D cells. Wildtype and T3SS mutants did not preferentially target different cell types identified within the 3-D intestinal aggregates, including M-cells/M-like cells, enterocytes, or Paneth cells. Moreover, each T3SS was necessary for substantial intracellular bacterial replication within 3-D cells. Collectively, these results indicate that T3SSs are dispensable for Salmonella invasion into highly differentiated 3-D models of human intestinal epithelial cells, but are required for intracellular bacterial growth, paralleling in vivo infection observations and demonstrating the utility of these models in predicting in vivo-like pathogenic mechanisms.
Authors:
Andrea L Radtke; James W Wilson; Shameema Sarker; Cheryl A Nickerson
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-12-29
Journal Detail:
Title:  PloS one     Volume:  5     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2010  
Date Detail:
Created Date:  2011-01-05     Completed Date:  2011-07-05     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e15750     Citation Subset:  IM    
Affiliation:
School of Life Sciences, Center for Infectious Diseases and Vaccinology, The Biodesign Institute at Arizona State University, Tempe, Arizona, United States of America.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Cells, Cultured
Gene Expression Profiling
Gene Expression Regulation, Bacterial
Humans
Imaging, Three-Dimensional
Intestinal Mucosa / cytology,  metabolism*
Mice
Mice, Knockout
Microscopy, Confocal / methods
Mutation*
Salmonella Infections / microbiology
Salmonella enterica / genetics*
Grant Support
ID/Acronym/Agency:
R21MH080702/MH/NIMH NIH HHS
Comments/Corrections

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