title: OatA, a peptidoglycan O-acetyltransferase involved in Listeria monocytogenes immune escape, is critical for virulence.
abstract: Microbial pathogens have evolved mechanisms to overcome immune responses and successfully infect their host. Here, we studied how Listeria monocytogenes evades immune detection by peptidoglycan (PGN) modification. By analyzing L. monocytogenes muropeptides, we detected O-acetylated muramic acid residues. We identified an O-acetyltransferase gene, oatA, in the L. monocytogenes genome sequence. Comparison of PGN from parental and isogenic oatA mutant strains showed that the O-acetyltransferase OatA O-acetylates Listeria PGN. We also found that PGN O-acetylation confers resistance to different types of antimicrobial compounds targeting bacterial cell wall such as lysozyme, β-lactam antibiotics, and bacteriocins and that O-acetylation is required for Listeria growth in macrophages. Moreover, oatA mutant virulence is drastically affected in mice following intravenous or oral inoculation. In addition, the oatA mutant induced early secretion of proinflammatory cytokines and chemokines in vivo. These results suggest an important role for OatA in limiting innate immune responses and promoting bacterial survival in the infected host.
authors.affiliation: Institut Pasteur, Département de Biologie Cellulaire et Infection, Unité des Interactions Bactéries-Cellules, Paris, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Aubry
authors.forename: Céline
authors.initials: C
authors.lastname: Goulard
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Nahori
authors.forename: Nadège
authors.initials: N
authors.lastname: Cayet
authors.forename: Jérémie
authors.initials: J
authors.lastname: Decalf
authors.forename: Martin
authors.initials: M
authors.lastname: Sachse
authors.forename: Ivo G
authors.initials: IG
authors.lastname: Boneca
authors.forename: Pascale
authors.initials: P
authors.lastname: Cossart
authors.forename: Olivier
authors.initials: O
authors.lastname: Dussurget
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000276:immunology*; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007928:Lethal Dose 50; D008089:Listeria monocytogenes / Q000235:genetics / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D008088:Listeriosis / Q000235:genetics / Q000276:immunology*; D008099:Liver / Q000378:metabolism / Q000382:microbiology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D009112:Muramic Acids / Q000378:metabolism; D010457:Peptidoglycan / Q000737:chemistry / Q000276:immunology*; D013154:Spleen / Q000382:microbiology; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; D009112:Muramic Acids; D010457:Peptidoglycan; D037521:Virulence Factors; D000123:Acetyltransferases