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Updated: Jul 9, 2026
Epithelial Cell Infection Analyses with Shigella
Published on: February 9, 2024
Muramylpeptide shedding modulates cell sensing of Shigella flexneri
Giulia Nigro1, Luigi Lembo Fazio, Maria Celeste Martino
1Dipartimento di Biologia Cellulare e dello Sviluppo, Sapienza-Università di Roma, Via dei Sardi 70, 00185 Roma, Italy.
Abstract:
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-kappaB 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.
Insights
Gram-negative pathogens like Shigella release peptidoglycan (PGN) fragments, which activate the innate immune receptor Nod1. Modulating PGN shedding influences host immune responses during infection.
Area of Science:
- Immunology
- Microbiology
- Molecular Biology
Background:
- Bacterial infections activate innate immunity via pathogen-associated molecular patterns (PAMPs) binding to pattern recognition molecules (PRMs).
- Nucleotide-binding oligomerization domain (Nod) proteins are intracellular PRMs recognizing bacterial peptidoglycan (PGN) muramylpeptides.
- The mechanism of Nod1 interaction with PGN in Gram-negative bacteria remains unclear.
Purpose of the Study:
- To investigate how Nod1 interacts with PGN from Gram-negative bacteria.
- To understand the role of PGN fragment shedding in Nod1-mediated immune activation.
- To explore how PGN shedding by Shigella influences host immune responses.
Main Methods:
- Analyzing PGN fragment release from wild-type and mutant Shigella strains (inactivating ampG or mppA).
- Measuring Nod1-mediated NF-kappaB activation in response to Shigella and its shed PGN fragments.
- Assessing in vivo host responses to Shigella infection with altered PGN shedding.
Main Results:
- Shigella spontaneously releases PGN fragments, with increased shedding in ampG and mppA mutants.
- Shed PGN fragments from Shigella activate Nod1-mediated NF-kappaB signaling.
- Mutants with altered PGN shedding exhibit differential Nod1 activation.
- Qualitative changes in shed muramylpeptides impact in vivo host responses.
Conclusions:
- Muramylpeptide release by Gram-negative pathogens is a mechanism for PGN interaction with Nod1.
- Pathogen-derived muramylpeptides can modulate host immune responses via Nod proteins.
- PGN shedding influences disease outcomes by affecting innate immunity.
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