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PMID: 15263085 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Discovery and characterization of sialic acid O-acetylation in group B Streptococcus.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 30 ·2004-07-27 ·Pages 11123-8

Lewis AL, Nizet V, Varki A

Abstract

Group B Streptococcus (GBS) is the leading cause of human neonatal sepsis and meningitis. The GBS capsular polysaccharide is a major virulence factor and the active principle of vaccines in phase II trials. All GBS capsules have a terminal alpha 2-3-linked sialic acid [N-acetylneuraminic acid (Neu5Ac)], which interferes with complement-mediated killing. We show here that some of the Neu5Ac residues of the GBS type III capsule are O-acetylated at carbon position 7, 8, or 9, a major modification evidently missed in previous studies. Data are consistent with initial O-acetylation at position 7, and subsequent migration of the O-acetyl ester at positions 8 and 9. O-acetylation was also present on several other GBS serotypes (Ia, Ib, II, V, and VI). Deletion of the CMP-Neu5Ac synthase gene neuA by precise, in-frame allelic replacement gave intracellular accumulation of O-acetylated Neu5Ac, whereas overexpression markedly decreased O-acetylation. Given the known GBS Neu5Ac biosynthesis pathway, these data indicate that O-acetylation occurs on free Neu5Ac, competing with the CMP-Neu5Ac synthase. O-acetylation often generates immunogenic epitopes on bacterial capsular polysaccharides and can modulate human alternate pathway complement activation. Thus, our discovery has important implications for GBS pathogenicity, immunogenicity, and vaccine design.

MeSH Terms
Acetic Acid/metabolism Acetylation Carbohydrate Conformation Carbohydrate Sequence Cell Wall/metabolism Cytidine Monophosphate N-Acetylneuraminic Acid/metabolism Mass Spectrometry Molecular Sequence Data N-Acetylneuraminic Acid/chemistry,metabolism Neuraminic Acids/chemistry,metabolism Polysaccharides, Bacterial/biosynthesis,chemistry Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Streptococcus agalactiae/metabolism beta-Galactosidase/metabolism
Chemicals
Neuraminic Acids Polysaccharides, Bacterial Cytidine Monophosphate N-Acetylneuraminic Acid beta-Galactosidase N-Acetylneuraminic Acid Acetic Acid
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Lewis Amanda L
Division of Biological Sciences, Glycobiology Research and Training Center, University of California at San Diego, La Jolla, CA 92093-0687, USA.
Nizet Victor
Varki Ajit
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0403010101
Published
2004-07-27
Epub
2004-00-19
Pages
11123-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC503750
Subset
IM
Grants
NHLBI NIH HHS · P01 HL057345 · United States
NIGMS NIH HHS · R01 GM032373 · United States
NIGMS NIH HHS · R01GM32373 · United States
NHLBI NIH HHS · R01HL57345 · United States
External Links
PubMed source DOI: 10.1073/pnas.0403010101 PMC Full Text View journal details
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