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Infection and Immunity, February 2009, p. 585-597, Vol. 77, No. 2
0019-9567/09/$08.00+0     doi:10.1128/IAI.01003-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Interaction of Enteric Bacterial Pathogens with Murine Embryonic Stem Cells {triangledown} ,{dagger}

Jun Yu,*{ddagger} Raffaella Rossi,{ddagger} Christine Hale, David Goulding, and Gordon Dougan

The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom

Received 11 August 2008/ Returned for modification 31 August 2008/ Accepted 13 November 2008

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.

* Corresponding author. Present address: Microbiology, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde Royal College, 204 George Street, Glasgow G1 1XW, Scotland. Phone: 44-141-548-2137. Fax: 44-141-553-4124. E-mail: jy1{at}sanger.ac.uk

{triangledown} Published ahead of print on 24 November 2008.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: A. J. Bäumler

{ddagger} J.Y. and R.R. contributed equally to this work.

Infection and Immunity, February 2009, p. 585-597, Vol. 77, No. 2
0019-9567/09/$08.00+0     doi:10.1128/IAI.01003-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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