critical role for peptidoglycan N-deacetylation in Listeria evasion from the host innate immune system

Listeria monocytogenes is a human intracellular pathogen that is able to survive in the gastrointestinal environment and replicate in macrophages, thus bypassing the early innate immune defenses. Peptidoglycan (PG) is an essential component of the bacterial cell wall readily exposed to the host and,...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2007-01, Vol.104 (3), p.997-1002
Main Authors: Boneca, Ivo G, Dussurget, Olivier, Cabanes, Didier, Nahori, Marie-Anne, Sousa, Sandra, Lecuit, Marc, Psylinakis, Emmanuel, Bouriotis, Vassilis, Hugot, Jean-Pierre, Giovannini, Marco, Coyle, Anthony, Bertin, John, Namane, Abdelkader, Rousselle, Jean-Claude, Cayet, Nadège, Prévost, Marie-Christine, Balloy, Viviane, Chignard, Michel, Philpott, Dana J, Cossart, Pascale, Girardin, Stephen E
Format: Article
Language:English
Subjects:
Acetylation
Amidohydrolases
Amidohydrolases - genetics
Amidohydrolases - metabolism
Animals
Bacteria
Bacteriology
Biological Sciences
Cell Line
Cell Survival
Cytokines
Genes
Gram-Positive Bacterial Infections
Gram-Positive Bacterial Infections - genetics
Gram-Positive Bacterial Infections - immunology
Gram-Positive Bacterial Infections - microbiology
Gram-Positive Bacterial Infections - pathology
Humans
Immune System
Immune System - immunology
Immunity, Innate - immunology
Immunity, Natural
Immunology
Infections
Innate immunity
Interleukin-6
Interleukin-6 - biosynthesis
Life Sciences
Listeria
Listeria - immunology
Listeria monocytogenes
Macrophages
Macrophages - cytology
Macrophages - immunology
Mice
Microbiology and Parasitology
Muramidase
Muramidase - metabolism
Mutation
Mutation - genetics
Pathogens
Pathology
Peptides
Peptidoglycan
Peptidoglycan - chemistry
Peptidoglycan - classification
Peptidoglycan - immunology
Peptidoglycan - metabolism
Phagocytes
Spectrometry, Mass, Matrix-Assi
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Vacuoles
Virulence
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Summary:Listeria monocytogenes is a human intracellular pathogen that is able to survive in the gastrointestinal environment and replicate in macrophages, thus bypassing the early innate immune defenses. Peptidoglycan (PG) is an essential component of the bacterial cell wall readily exposed to the host and, thus, an important target for the innate immune system. Characterization of the PG from L. monocytogenes demonstrated deacetylation of N-acetylglucosamine residues. We identified a PG N-deacetylase gene, pgdA, in L. monocytogenes genome sequence. Inactivation of pgdA revealed the key role of this PG modification in bacterial virulence because the mutant was extremely sensitive to the bacteriolytic activity of lysozyme, and growth was severely impaired after oral and i.v. inoculations. Within macrophage vacuoles, the mutant was rapidly destroyed and induced a massive IFN-β response in a TLR2 and Nod1-dependent manner. Together, these results reveal that PG N-deacetylation is a highly efficient mechanism used by Listeria to evade innate host defenses. The presence of deacetylase genes in other pathogenic bacteria indicates that PG N-deacetylation could be a general mechanism used by bacteria to evade the host innate immune system.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0609672104