Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 111, Issue 4, Pages 1574-1579Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1317181111
Keywords
surface protein; Gram-positive bacteria; sortase-anchored protein
Categories
Funding
- US National Institute of Allergy and Infectious Diseases, Infectious Diseases Branch [AI052474, AI038897]
- Region V Great Lakes Regional Center of Excellence in Biodefense and Emerging Infectious Diseases Consortium (National Institutes of Health) [1-U54-AI-057153]
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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., Gly(5)). SpA binds the Fc gamma 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-Gly(5))L-Lys-D-Ala-Gly(4)] 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-acetyl-glucosamine (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.
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