Document Detail

Genetic and biochemical modulation of sialic acid O-acetylation on group B Streptococcus: phenotypic and functional impact.
MedLine Citation:
PMID:  19643844     Owner:  NLM     Status:  MEDLINE    
Group B Streptococcus (GBS) is an important human pathogen and a model system for studying the roles of bacterial glycosylation in host-microbe interactions. Sialic acid (Sia), expressed prominently in the GBS capsular polysaccharide (CPS), mimics mammalian cell surface Sia and can interact with host Sia-binding proteins to subvert immune clearance mechanisms. Our earlier work has shown that GBS partially O-acetylates CPS Sia residues and employs an intracellular O-acetylation/de-O-acetylation cycle to control the final level of this surface Sia modification. Here, we examine the effects of point mutations in the NeuD O-acetyltransferase and NeuA O-acetylesterase on specific glycosylation phenotypes of GBS, pinpointing an isogenic strain pair that differs dramatically in the degree of the O-acetyl modification (80% versus 5%) while still expressing comparable levels of overall sialylation. Using these strains, higher levels of O-acetylation were found to protect GBS CPS Sia against enzymatic removal by microbial sialidases and to impede engagement of human Siglec-9, but not to significantly alter the ability of GBS to restrict complement C3b deposition on its surface. Additional experiments demonstrated that pH-induced migration of the O-acetyl modification from the 7- to 9-carbon position had a substantial impact on GBS-Siglec-9 interactions, with 7-O-acetylation exhibiting the strongest interference. These studies show that both the degree and position of the GBS O-acetyl modification influence Sia-specific interactions relevant to the host-pathogen relationship. We conclude that native GBS likely expresses a phenotype of intermediate Sia O-acetylation to strike a balance between competing selective pressures present in the host environment.
Shannon Weiman; Samira Dahesh; Aaron F Carlin; Ajit Varki; Victor Nizet; Amanda L Lewis
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-07-30
Journal Detail:
Title:  Glycobiology     Volume:  19     ISSN:  1460-2423     ISO Abbreviation:  Glycobiology     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-10-07     Completed Date:  2010-02-25     Revised Date:  2013-06-10    
Medline Journal Info:
Nlm Unique ID:  9104124     Medline TA:  Glycobiology     Country:  England    
Other Details:
Languages:  eng     Pagination:  1204-13     Citation Subset:  IM    
Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093-0687, USA.
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MeSH Terms
N-Acetylneuraminic Acid / chemistry*,  metabolism*
Streptococcus agalactiae / classification,  enzymology,  genetics*,  metabolism*
Grant Support
Reg. No./Substance:
131-48-6/N-Acetylneuraminic Acid

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