title: A critical role for peptidoglycan N-deacetylation in Listeria evasion from the host innate immune system.
abstract: 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-beta 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.
authors.affiliation: Unité de Pathogénie Bactérienne des Muqueuses, Institut Pasteur, 75724 Paris, France. bonecai@pasteur.fr
authors.forename: Ivo G
authors.initials: IG
authors.lastname: Boneca
authors.forename: Olivier
authors.initials: O
authors.lastname: Dussurget
authors.forename: Didier
authors.initials: D
authors.lastname: Cabanes
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Nahori
authors.forename: Sandra
authors.initials: S
authors.lastname: Sousa
authors.forename: Marc
authors.initials: M
authors.lastname: Lecuit
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Psylinakis
authors.forename: Vassilis
authors.initials: V
authors.lastname: Bouriotis
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hugot
authors.forename: Marco
authors.initials: M
authors.lastname: Giovannini
authors.forename: Anthony
authors.initials: A
authors.lastname: Coyle
authors.forename: John
authors.initials: J
authors.lastname: Bertin
authors.forename: Abdelkader
authors.initials: A
authors.lastname: Namane
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Rousselle
authors.forename: Nadège
authors.initials: N
authors.lastname: Cayet
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Prévost
authors.forename: Viviane
authors.initials: V
authors.lastname: Balloy
authors.forename: Michel
authors.initials: M
authors.lastname: Chignard
authors.forename: Dana J
authors.initials: DJ
authors.lastname: Philpott
authors.forename: Pascale
authors.initials: P
authors.lastname: Cossart
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Girardin
mesh_terms: D000107:Acetylation; D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D016908:Gram-Positive Bacterial Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D006801:Humans; D007107:Immune System / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D015850:Interleukin-6 / Q000096:biosynthesis; D008087:Listeria / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D009113:Muramidase / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010457:Peptidoglycan / Q000737:chemistry / Q000145:classification / Q000276:immunology* / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015850:Interleukin-6; D010457:Peptidoglycan; D009113:Muramidase; D000581:Amidohydrolases