Genetic and biochemical modulation of sialic acid O-acetylation on group B Streptococcus: Phenotypic and functional impact

AUTOR(ES)

Weiman, Shannon

FONTE

Oxford University Press

RESUMO

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.

Documentos Relacionados

• Discovery and characterization of sialic acid O-acetylation in group B Streptococcus
• Influence of protein synthesis inhibitors on regulation of extent of O-acetylation of gonococcal peptidoglycan.
• Strain-related differences in lysozyme sensitivity and extent of O-acetylation of gonococcal peptidoglycan.
• O-acetylation of a cell-surface carbohydrate creates discrete molecular patterns during neural development.
• Strain distribution in extents of lysozyme resistance and O-acetylation of gonococcal peptidoglycan determined by high-performance liquid chromatography.