Interaction of enteric bacterial pathogens with murine embryonic stem cells
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Published on: October 29, 2014
Jun Yu1, Raffaella Rossi, Christine Hale
1The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom. jy1@sanger.ac.uk
Abstract:
Embryonic stem (ES) cells are susceptible to genetic manipulation and retain the potential to differentiate into diverse cell types, which are factors that make them potentially attractive cells for studying host-pathogen interactions. Murine ES cells were found to be susceptible to invasion by Salmonella enterica serovar Typhimurium and Shigella flexneri and to the formation of attaching and effacing lesions by enteropathogenic Escherichia coli. S. enterica serovar Typhimurium and S. flexneri cell entry was dependent on the Salmonella pathogenicity island 1 and Shigella mxi/spa type III secretion systems, respectively. Microscopy studies indicated that both S. enterica serovar Typhimurium and S. flexneri were located in intracellular niches in ES cells that were similar to the niches occupied in differentiated cells. ES cells were eventually killed following bacterial invasion, but no evidence of activation of classical caspase-associated apoptotic or innate immune pathways was found. To demonstrate the potential of mutant ES cells, we employed an ES cell line defective in cholesterol synthesis and found that the mutant cells were less susceptible to infection by Salmonella and Shigella than the parental ES cells. Thus, we highlighted the practical use of genetically modified ES cells for studying microbe-host interactions.
Insights
Embryonic stem cells are vulnerable to bacterial invasion, including Salmonella and Shigella. Genetically modified stem cells offer a novel approach for studying these microbe-host interactions.
Area of Science:
- Microbiology
- Stem Cell Biology
- Infectious Diseases
Background:
- Embryonic stem (ES) cells possess unique properties, including genetic manipulability and differentiation potential, making them valuable models for biological research.
- Understanding host-pathogen interactions is crucial for developing effective therapeutic strategies against infectious diseases.
Purpose of the Study:
- To investigate the susceptibility of murine embryonic stem cells to invasion by pathogenic bacteria.
- To explore the mechanisms of bacterial entry and intracellular survival within ES cells.
- To evaluate the utility of genetically modified ES cells in studying host-pathogen dynamics.
Main Methods:
- Murine ES cells were infected with Salmonella enterica serovar Typhimurium, Shigella flexneri, and enteropathogenic Escherichia coli.
- Invasion mechanisms were assessed using genetic mutants deficient in specific bacterial virulence factors, including type III secretion systems.
- Intracellular localization and host cell responses were examined using microscopy.
- A cholesterol synthesis-deficient ES cell line was utilized to assess the role of cholesterol in host susceptibility.
Main Results:
- Murine ES cells were susceptible to invasion by Salmonella Typhimurium and Shigella flexneri, and to lesion formation by enteropathogenic E. coli.
- Bacterial entry was dependent on specific virulence factors, namely the Salmonella pathogenicity island 1 and Shigella mxi/spa type III secretion systems.
- Intracellular bacteria resided in niches similar to those observed in differentiated cells.
- ES cells succumbed to bacterial invasion without activation of classical apoptotic or innate immune pathways.
- A cholesterol synthesis-deficient ES cell line exhibited reduced susceptibility to Salmonella and Shigella infection.
Conclusions:
- Embryonic stem cells serve as a viable model for studying bacterial invasion and intracellular pathogenesis.
- The study highlights the practical application of genetically modified ES cells for dissecting microbe-host interactions.
- Defects in host cell pathways, such as cholesterol synthesis, can confer resistance to bacterial pathogens.
