Present address: University of Toronto, Toronto, Canada.
Muramylpeptide shedding modulates cell sensing of Shigella flexneri
Article first published online: 23 OCT 2007
Journal compilation © 2007 Blackwell Publishing Ltd; No claim to original US government works
Volume 10, Issue 3, pages 682–695, March 2008
How to Cite
Nigro, G., Fazio, L. L., Martino, M. C., Rossi, G., Tattoli, I., Liparoti, V., De Castro, C., Molinaro, A., Philpott, D. J. and Bernardini, M. L. (2008), Muramylpeptide shedding modulates cell sensing of Shigella flexneri. Cellular Microbiology, 10: 682–695. doi: 10.1111/j.1462-5822.2007.01075.x
- Issue published online: 23 OCT 2007
- Article first published online: 23 OCT 2007
- Received 18 September, 2007; revised 4 October, 2007; accepted 4 October, 2007.
Bacterial infections trigger the activation of innate immunity through the interaction of pathogen-associated molecular patterns (PAMPs) with pattern recognition molecules (PRMs). The nucleotide-binding oligomerization domain (Nod) proteins are intracellular PRMs that recognize muramylpeptides contained in peptidoglycan (PGN) of bacteria. It is still unclear how Nod1 physically interacts with PGN, a structure internal to the Gram-negative bacterial envelope. To contribute to the understanding of this process, we demonstrate that, like Escherichia coli, Bordetella pertussis and Neisseria gonorrheae, the Gram-negative pathogen Shigella spontaneously releases PGN fragments and that this process can be increased by inactivating either ampG or mppA, genes involved in PGN recycling. Both Shigella mutants, but especially the strain carrying the mppA deletion, trigger Nod1-mediated NF-κB activation to a greater extent than the wild-type strain. Likewise, muramylpeptides spontaneously shed by Shigella are able per se to trigger a Nod1-mediated response consistent with the relative amount. Finally, we found that qualitative changes in muramylpeptide shedding can alter in vivo host responses to Shigella infection. Our findings support the idea that muramylpeptides released by pathogens during infection could modulate the immune response through Nod proteins and thereby influence the outcome of disease.