title: Staphylococcus aureus evades lysozyme-based peptidoglycan digestion that links phagocytosis, inflammasome activation, and IL-1beta secretion.
abstract: IL-1beta produced by phagocytes is important for protection against the mucosal pathogen Staphylococcus aureus. Processing and maturation of this cytokine requires activation of the multiprotein inflammasome complex. We observed that the bacterial cell wall component peptidoglycan (PGN) must be particulate and internalized via phagocytosis to activate NLRP3 inflammasomes and IL-1beta secretion. In the context of S. aureus infection of macrophages, we find that phagocytosis and lysozyme-based bacterial cell wall degradation are necessary to induce IL-1beta secretion. Further, an S. aureus enzyme, PGN O-acetyltransferase A, previously demonstrated to make cell wall PGN resistant to lysozyme, strongly suppresses inflammasome activation and inflammation in vitro and in vivo. These observations demonstrate that phagocytosis and lysozyme-based cell wall degradation of S. aureus are functionally coupled to inflammasome activation and IL-1beta secretion and illustrate a case whereby a bacterium specifically subverts IL-1beta secretion through chemical modification of its cell wall PGN.
authors.affiliation: Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shimada
authors.forename: Bong Goo
authors.initials: BG
authors.lastname: Park
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Wolf
authors.forename: Constantinos
authors.initials: C
authors.lastname: Brikos
authors.forename: Helen S
authors.initials: HS
authors.lastname: Goodridge
authors.forename: Courtney A
authors.initials: CA
authors.lastname: Becker
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Reyes
authors.forename: Edward A
authors.initials: EA
authors.lastname: Miao
authors.forename: Alan
authors.initials: A
authors.lastname: Aderem
authors.forename: Friedrich
authors.initials: F
authors.lastname: Götz
authors.forename: George Y
authors.initials: GY
authors.lastname: Liu
authors.forename: David M
authors.initials: DM
authors.lastname: Underhill
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D008954:Models, Biological; D009113:Muramidase / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010457:Peptidoglycan / Q000378:metabolism*; D010588:Phagosomes / Q000201:enzymology*; D013211:Staphylococcus aureus / Q000737:chemistry / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D010457:Peptidoglycan; D009113:Muramidase