title: N-acetylglucosaminylation of serine-aspartate repeat proteins promotes Staphylococcus aureus bloodstream infection.
abstract: Staphylococcus aureus secretes products that convert host fibrinogen to fibrin and promote its agglutination with fibrin fibrils, thereby shielding bacteria from immune defenses. The agglutination reaction involves ClfA (clumping factor A), a surface protein with serine-aspartate (SD) repeats that captures fibrin fibrils and fibrinogen. Pathogenic staphylococci express several different SD proteins that are modified by two glycosyltransferases, SdgA and SdgB. Here, we characterized three genes of S. aureus, aggA, aggB (sdgA), and aggC (sdgB), and show that aggA and aggC contribute to staphylococcal agglutination with fibrin fibrils in human plasma. We demonstrate that aggB (sdgA) and aggC (sdgB) are involved in GlcNAc modification of the ClfA SD repeats. However, only sdgB is essential for GlcNAc modification, and an sdgB mutant is defective in the pathogenesis of sepsis in mice. Thus, GlcNAc modification of proteins promotes S. aureus replication in the bloodstream of mammalian hosts.
authors.affiliation: From the Department of Microbiology, The University of Chicago, Chicago, Illinois 60637 and.
authors.forename: Lena
authors.initials: L
authors.lastname: Thomer
authors.forename: Samuel
authors.initials: S
authors.lastname: Becker
authors.forename: Carla
authors.initials: C
authors.lastname: Emolo
authors.forename: Austin
authors.initials: A
authors.lastname: Quach
authors.forename: Hwan Keun
authors.initials: HK
authors.lastname: Kim
authors.forename: Sabine
authors.initials: S
authors.lastname: Rauch
authors.forename: Mark
authors.initials: M
authors.lastname: Anderson
authors.forename: James F
authors.initials: JF
authors.lastname: Leblanc
authors.forename: Olaf
authors.initials: O
authors.lastname: Schneewind
authors.forename: Kym F
authors.initials: KF
authors.lastname: Faull
authors.forename: Dominique
authors.initials: D
authors.lastname: Missiakas
mesh_terms: D000117:Acetylglucosamine / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000371:Agglutination; D000818:Animals; D003030:Coagulase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005337:Fibrin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005964:Glucosyltransferases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D051379:Mice; D013203:Staphylococcal Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: C515944:ClfA protein, Staphylococcus aureus; D003030:Coagulase; D005337:Fibrin; D005964:Glucosyltransferases; D000117:Acetylglucosamine
keywords: Agglutination; ClfA; Coagulation Factors; Fibrin; Glycosyltransferases; Infectious Diseases; Serine-Aspartate Repeat; Staphylococcus aureus