title: Release of protein A from the cell wall of Staphylococcus aureus.
abstract: Staphylococcal protein A (SpA) is anchored to the cell wall envelope of Staphylococcus aureus by sortase A, which links the threonyl (T) of its C-terminal LPXTG motif to peptidoglycan cross-bridges (i.e., Gly5). SpA binds the Fcγ domains of IgG and protects staphylococci from opsonophagocytic clearance. Moreover, SpA cross-links B-cell receptors to modify host adaptive immune responses. The mechanisms whereby SpA is released from the bacterial surface to access the host's immune system are not known. Here we demonstrate that SpA is released with murein tetrapeptide-tetraglycyl [L-Ala-D-iGln-(SpA-Gly5)L-Lys-D-Ala-Gly4] linked to its C-terminal threonyl. LytN, a cross-wall murein hydrolase, contributes to the release of SpA by removing amino sugars [i.e., N-acetylmuramic acid-N-acetylglucosamine (MurNAc-GlcNAc)] from attached peptidoglycan, whereas LytM, a pentaglycyl-endopeptidase, triggers polypeptide release from the bacterial envelope. A model is proposed whereby murein hydrolases cleave the anchor structure of released SpA to modify host immune responses.
authors.affiliation: Department of Microbiology, University of Chicago, Chicago, IL 60637.
authors.forename: Samuel
authors.initials: S
authors.lastname: Becker
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Frankel
authors.forename: Olaf
authors.initials: O
authors.lastname: Schneewind
authors.forename: Dominique
authors.initials: D
authors.lastname: Missiakas
mesh_terms: D000595:Amino Acid Sequence; D002473:Cell Wall / Q000378:metabolism*; D008969:Molecular Sequence Data; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013205:Staphylococcal Protein A / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000378:metabolism*
chemical_list: D013205:Staphylococcal Protein A
keywords: Gram-positive bacteria; sortase-anchored protein; surface protein