Structure of the Type IX Group B Streptococcus Capsular Polysaccharide and Its Evolutionary Relationship with Types V and VII

Berti, Francesco; Campisi, Edmondo; Toniolo, Chiara; Morelli, Laura; Crotti, Stefano; Rosini, Roberto; Romano, Maria; Pinto, Vittoria; Brogioni, Barbara; Torricelli, Giulia; Janulczyk, Robert; Grandi, Guido; Margarit, Immaculada

doi:10.1074/jbc.m114.567974

Cited by 51 publications

(48 citation statements)

References 36 publications

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“…Almost all GBS strains associated with human disease are encapsulated, belonging to 1 of 10 capsular types recognized by specific Abs: Ia, Ib, and II-IX. The 10 GBS capsular polysaccharide structures are created by diverse arrangements of galactose, glucose, N-acetylglucosamine, and sialic acid into unique repeating units that invariably contain sialic acid on their branching terminus (5). Type III GBS, frequently found in neonatal invasive infections, expresses a large amount of capsular polysaccharide that was shown to inhibit activation of the complement AP in adult sera deficient in specific Abs (6), whereas AP inhibition could be overcome by anti-type III polysaccharide IgG (7).…”

Section: S Treptococcus Agalactiae (Group B Streptococcus [Gbs])mentioning

confidence: 99%

The Group B Streptococcus–Secreted Protein CIP Interacts with C4, Preventing C3b Deposition via the Lectin and Classical Complement Pathways

Pietrocola

Rindi

Rosini³

et al. 2016

The Journal of Immunology

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The group B Streptococcus (GBS) is a leading cause of neonatal invasive disease. GBS bacteria are surrounded by a thick capsular polysaccharide that is a potent inhibitor of complement deposition via the alternative pathway. Several of its surface molecules can however activate the classical and lectin complement pathways, rendering this species still vulnerable to phagocytic killing. In this study we have identified a novel secreted protein named complement interfering protein (CIP) that downregulates complement activation via the classical and lectin pathways, but not the alternative pathway. The CIP protein showed high affinity toward C4b and inhibited its interaction with C2, presumably preventing the formation of the C4bC2a convertase. Addition of recombinant CIP to GBS cip-negative bacteria resulted in decreased deposition of C3b on their surface and in diminished phagocytic killing in a whole-blood assay. Our data reveal a novel strategy exploited by GBS to counteract innate immunity and could be valuable for the development of anti-infective agents against this important pathogen.

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Section: S Treptococcus Agalactiae (Group B Streptococcus [Gbs])mentioning

confidence: 99%

The Group B Streptococcus–Secreted Protein CIP Interacts with C4, Preventing C3b Deposition via the Lectin and Classical Complement Pathways

Pietrocola

Rindi

Rosini³

et al. 2016

The Journal of Immunology

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“…[4][5][6][7][8] They are high molecular weight antigens with repeating epitopes that are displayed on bacterial and fungal cell surfaces. [9][10][11][12] The B. pseudomallei CPS is comprised of an unbranched homopolymer of 1,3-linked 2-O-acetyl-6-deoxy-b-D-mannoheptopyranose residues. 13 CPS has been shown to inhibit phagocytosis by reducing the amount of complement factor C3b that is deposited on the bacterial cell surface.…”

Section: Introductionmentioning

confidence: 99%

Contribution of murine IgG Fc regions to antibody binding to the capsule ofBurkholderia pseudomallei

et al. 2016

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“…The GBS capsular PS is constituted by multiple RUs (from ∼50 up to 300 per polymer) of four to seven monosaccharides shaped to form a backbone and one or two side chains. Ten serotypes presenting a unique pattern of glycosidic linkages have been identified and their primary structures elucidated (13). Three monosaccharides (β-D-glucopyranose, β-D-Glc; β-D-galactopyranose, β-D-Gal; and β-D-N-acetylglucosamine, β-D-GlcNAc) are present in all of the described serotypes, and sialic acid (α-N-acetyl-neuraminic acid, NeuNAc) is always found at the terminus of one chain (13).…”

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confidence: 99%

Structure of a protective epitope of group BStreptococcustype III capsular polysaccharide

Carboni¹,

Adamo²,

Fabbrini³

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Despite substantial progress in the prevention of group B Streptococcus (GBS) disease with the introduction of intrapartum antibiotic prophylaxis, this pathogen remains a leading cause of neonatal infection. Capsular polysaccharide conjugate vaccines have been tested in phase I/II clinical studies, showing promise for further development. Mapping of epitopes recognized by protective antibodies is crucial for understanding the mechanism of action of vaccines and for enabling antigen design. In this study, we report the structure of the epitope recognized by a monoclonal antibody with opsonophagocytic activity and representative of the protective response against type III GBS polysaccharide. The structure and the atomic-level interactions were determined by saturation transfer difference (STD)-NMR and X-ray crystallography using oligosaccharides obtained by synthetic and depolymerization procedures. The GBS PSIII epitope is made by six sugars. Four of them derive from two adjacent repeating units of the PSIII backbone and two of them from the branched galactose–sialic acid disaccharide contained in this sequence. The sialic acid residue establishes direct binding interactions with the functional antibody. The crystal structure provides insight into the molecular basis of antibody–carbohydrate interactions and confirms that the conformational epitope is not required for antigen recognition. Understanding the structural basis of immune recognition of capsular polysaccharide epitopes can aid in the design of novel glycoconjugate vaccines.

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Structure of the Type IX Group B Streptococcus Capsular Polysaccharide and Its Evolutionary Relationship with Types V and VII

Cited by 51 publications

References 36 publications

The Group B Streptococcus–Secreted Protein CIP Interacts with C4, Preventing C3b Deposition via the Lectin and Classical Complement Pathways

The Group B Streptococcus–Secreted Protein CIP Interacts with C4, Preventing C3b Deposition via the Lectin and Classical Complement Pathways

Contribution of murine IgG Fc regions to antibody binding to the capsule ofBurkholderia pseudomallei

Structure of a protective epitope of group BStreptococcustype III capsular polysaccharide

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