title: Host defenses against Staphylococcus aureus infection require recognition of bacterial lipoproteins.
abstract: Toll-like receptors and other immune-signaling pathways play important roles as sensors of bacterial pattern molecules, such as peptidoglycan, lipoprotein, or teichoic acid, triggering innate host immune responses that prevent infection. Immune recognition of multiple bacterial products has been viewed as a safeguard against stealth infections; however, this hypothesis has never been tested for Staphylococcus aureus, a frequent human pathogen. By generating mutations that block the diacylglycerol modification of lipoprotein precursors, we show here that S. aureus variants lacking lipoproteins escape immune recognition and cause lethal infections with disseminated abscess formation, failing to elicit an adequate host response. Thus, lipoproteins appear to play distinct, nonredundant roles in pathogen recognition and host innate defense mechanisms against S. aureus infections.
authors.affiliation: Department of Microbiology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Juliane
authors.initials: J
authors.lastname: Bubeck Wardenburg
authors.forename: Wade A
authors.initials: WA
authors.lastname: Williams
authors.forename: Dominique
authors.initials: D
authors.lastname: Missiakas
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D007668:Kidney / Q000382:microbiology / Q000473:pathology; D008074:Lipoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008099:Liver / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D013203:Staphylococcal Infections / Q000276:immunology* / Q000473:pathology; D013211:Staphylococcus aureus / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity*; D014166:Transferases / Q000235:genetics*; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D008074:Lipoproteins; D014166:Transferases; C042308:phosphatidylglycerol glyceryl transferase