Synthesis and NMR assignment of two repeating units (decasaccharide) of the type III group B Streptococcus capsular polysaccharide and its13 C-labeled and N-propionyl substituted sialic acid analogues

1996 ◽  
Vol 295 (1-4) ◽  
pp. 209-228
Author(s):  
Z Wei
Keyword(s):  
Sialic Acid ◽  
Nmr Assignment ◽  
Capsular Polysaccharide ◽  
Group B Streptococcus ◽  
Type Iii ◽  
Sialic Acid Analogues ◽  
Group B

scholarly journals Immunodeterminant specificity of human immunity to type III group B streptococcus.

1979 ◽  
Vol 149 (2) ◽  
pp. 327-339 ◽  
Author(s):  
D L Kasper ◽  
C J Baker ◽  
R S Baltimore ◽  
J H Crabb ◽  
G Schiffman ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Capsular Polysaccharide ◽  
Group B Streptococcus ◽  
Core Antigen ◽  
Opsonic Activity ◽  
Type Iii ◽  
The Core ◽  
Native Antigen ◽  
Group B ◽  
Native Group

The type III polysaccharides of group B Streptococcus in its native state chemically consists of glucose, galactose, glucosamine, and sialic acid. The core of this polysaccharide lacks sialic acid and precipitates with type III antiserum to give a partial identity with the precipitate between the native antigen and this serum. The core determinant is immunochemically similar to the capsular polysaccharide of type XIV Streptococcus pneumoniae, while the native type III group B streptococcal polysaccharide does not cross-react with type XIV pneumococcal antiserum. In human sera, it is antibody directed to the native antigen which correlates very highly with opsonic immunity (r = 0.94) while a poorer correlation exists between antibody to the core antigen and opsonins (r = 0.51 P less than 0.001). In natural infections, as association exists between low levels of maternal antibody to the native antigen and risk of disease in the infant. This association is not true for antibody to the core structure, where both infected infants and their mothers have much higher levels of antibody to the core than the native antigens. Infected infants are also more likely to respond to infection by developing antibody to the native antigen. Immunization of 12 adults with multivalent pneumococcal polysaccharide induced significantly better antibody response to the core antigen than to the native, and this vaccine induced opsonic activity in only one recipient. Immunization of adults with type III group B streptococcal antigens induced antibody to the native determinant which correlated with opsonic activity. Therefore, it would appear that native group B streptococcal polysaccharides will provide the best candidate antigens for immunization.

Synthesis of Group B Streptococcus type III polysaccharide fragments for evaluation of their interactions with monoclonal antibodies

2017 ◽  
Vol 89 (7) ◽  
pp. 855-875 ◽  
Author(s):  
Vittorio Cattaneo ◽  
Filippo Carboni ◽  
Davide Oldrini ◽  
Riccardo De Ricco ◽  
Nunzio Donadio ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Sialic Acid ◽  
Capsular Polysaccharide ◽  
Group B Streptococcus ◽  
Sialic Acid Residue ◽  
Dependent Manner ◽  
Helical Structures ◽  
Type Iii ◽  
Antibody Recognition ◽  
Group B

AbstractGroup B Streptococcus type III (GBSIII) is the most relevant serotype among GBS strains causing infections and the potential of its capsular polysaccharide conjugated to a protein carrier as vaccine is well documented. Polysaccharide from GBSIII (PSIII) can form helical structures in solution where negatively charged sialic acid residues would be disposed externally providing stabilization to the helix. A peculiar high affinity to specific monoclonal antibodies (mAbs) has been reported for PSIII, and fragments of diverse size bind to mAbs in a length dependent manner. These data have been rationalized in terms of conformational epitopes that would be formed by fragments with >4 saccharidic repeating units. Saturation Transfer Difference NMR experiments have demonstrated that the sialic acid residue is not involved in antibody recognition. However the molecular basis of the interaction between PSIII and mAbs has not been fully elucidated. An important prerequisite to achieve this would be the availability of the three possible sugar sequences representing the pentasaccharide PSIII repeating unit. Herein we established a [2+3] convergent approach leading to these three pentasaccharides (1–3) with the end terminal sugar bearing a linker for possible conjugation. The PSIII fragments were coupled to the genetically detoxified diphtheria toxin CRM197 to prove by ELISA that the three pentasaccharides are recognized by polyclonal anti-PSIII serum. The presence of the branching formed by a Glc residue β-(1→6) linked to GlcNAc was proven an important motif for antibody recognition.

scholarly journals NeuA Sialic Acid O-Acetylesterase Activity Modulates O-Acetylation of Capsular Polysaccharide in Group B Streptococcus

2007 ◽  
Vol 282 (38) ◽  
pp. 27562-27571 ◽  
Author(s):  
Amanda L. Lewis ◽  
Hongzhi Cao ◽  
Silpa K. Patel ◽  
Sandra Diaz ◽  
Wesley Ryan ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Capsular Polysaccharide ◽  
Group B Streptococcus ◽  
Site Directed Mutagenesis ◽  
Synthetase Activity ◽  
Bacterial Surface ◽  
Acetylneuraminic Acid ◽  
Single Polypeptide ◽  
Group B

Group B Streptococcus (GBS) is a common cause of neonatal sepsis and meningitis. A major GBS virulence determinant is its sialic acid (Sia)-capped capsular polysaccharide. Recently, we discovered the presence and genetic basis of capsular Sia O-acetylation in GBS. We now characterize a GBS Sia O-acetylesterase that modulates the degree of GBS surface O-acetylation. The GBS Sia O-acetylesterase operates cooperatively with the GBS CMP-Sia synthetase, both part of a single polypeptide encoded by the neuA gene. NeuA de-O-acetylation of free 9-O-acetyl-N-acetylneuraminic acid (Neu5,9Ac2) was enhanced by CTP and Mg2+, the substrate and co-factor, respectively, of the N-terminal GBS CMP-Sia synthetase domain. In contrast, the homologous bifunctional NeuA esterase from Escherichia coli K1 did not display cofactor dependence. Further analyses showed that in vitro, GBS NeuA can operate via two alternate enzymatic pathways: de-O-acetylation of Neu5,9Ac2 followed by CMP activation of Neu5Ac or activation of Neu5,9Ac2 followed by de-O-acetylation of CMP-Neu5,9Ac2. Consistent with in vitro esterase assays, genetic deletion of GBS neuA led to accumulation of intracellular O-acetylated Sias, and overexpression of GBS NeuA reduced O-acetylation of Sias on the bacterial surface. Site-directed mutagenesis of conserved asparagine residue 301 abolished esterase activity but preserved CMP-Sia synthetase activity, as evidenced by hyper-O-acetylation of capsular polysaccharide Sias on GBS expressing only the N301A NeuA allele. These studies demonstrate a novel mechanism regulating the extent of capsular Sia O-acetylation in intact bacteria and provide a genetic strategy for manipulating GBS O-acetylation in order to explore the role of this modification in GBS pathogenesis and immunogenicity.

scholarly journals Capsular Sialic Acid Limits C5a Production on Type III Group B Streptococci

1999 ◽  
Vol 67 (4) ◽  
pp. 1866-1870 ◽  
Author(s):  
Shinji Takahashi ◽  
Youko Aoyagi ◽  
Elisabeth E. Adderson ◽  
Yoshiyuki Okuwaki ◽  
John F. Bohnsack
Keyword(s):  
Sialic Acid ◽  
Specific Antibody ◽  
Acid Content ◽  
Alternative Pathway ◽  
Group B Streptococcus ◽  
Neonatal Infections ◽  
Group B Streptococci ◽  
Sialic Acid Content ◽  
Type Iii ◽  
Group B

ABSTRACT The majority of type III group B streptococcus (GBS) human neonatal infections are caused by a genetically related subgroup called III-3. We have proposed that a bacterial enzyme, C5a-ase, contributes to the pathogenesis of neonatal infections with GBS by rapidly inactivating C5a, a potent pro-inflammatory molecule, but many III-3 strains do not express C5a-ase. The amount of C5a produced in serum following incubation with representative type III strains was quantitated in order to better understand the relationship between C5a production and C5a-ase expression. C5a production following incubation of bacteria with serum depleted of antibody to the bacterial surface was inversely proportional to the sialic acid content of the bacterial capsule, with the more heavily sialylated III-3 strains generating less C5a than the less-virulent, less-sialylated III-2 strains. The amount of C5a produced correlated significantly with C3 deposition on each bacterial strain. Repletion with type-specific antibody caused increased C3b deposition and C5a production through alternative pathway activation, but C5a was functionally inactivated by strains that expressed C5a-ase. The increased virulence of III-3 strains compared to that of III-2 strains results at least partially from the higher sialic acid content of III-3 strains, which inhibits both opsonophagocytic killing and C5a production in the absence of type-specific antibody. We propose that C5a-ase is not necessary for III-3 strains to cause invasive disease because the high sialic acid content of III-3 strains inhibits C5a production.

scholarly journals A Phase 2, Randomized, Control Trial of Group B Streptococcus (GBS) Type III Capsular Polysaccharide-tetanus Toxoid (GBS III-TT) Vaccine to Prevent Vaginal Colonization With GBS III

2018 ◽  
Vol 68 (12) ◽  
pp. 2079-2086 ◽  
Author(s):  
Sharon L Hillier ◽  
Patricia Ferrieri ◽  
Morven S Edwards ◽  
Marian Ewell ◽  
Daron Ferris ◽  
...  
Keyword(s):  
Tetanus Toxoid ◽  
Capsular Polysaccharide ◽  
Geometric Mean ◽  
Group B Streptococcus ◽  
Fold Increase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Type Iii ◽  
Maternal Immunization ◽  
Young Infants ◽  
Group B

Abstract Background Group B Streptococcus (GBS) frequently colonizes pregnant women and can cause sepsis and meningitis in young infants. If colonization was prevented through maternal immunization, a reduction in perinatal GBS disease might be possible. A GBS type III capsular polysaccharide (CPS)-tetanus toxoid conjugate (III-TT) vaccine was evaluated for safety and efficacy in preventing acquisition of GBS colonization. Methods Healthy, nonpregnant women aged 18–40 years and screened to be GBS III vaginal and rectal culture negative were randomized to receive III-TT conjugate or tetanus diphtheria toxoid vaccine in a multicenter, observer-blinded trial. GBS vaginal and rectal cultures and blood were obtained bimonthly over 18 months. Serum concentrations of GBS III CPS-specific antibodies were determined using enzyme-linked immunosorbent assay. Results Among 1525 women screened, 650 were eligible for the intent-to-treat analysis. For time to first acquisition of vaginal GBS III, vaccine efficacy was 36% (95% confidence interval [CI], 1%–58%; P = .044), and for first rectal acquisition efficacy was 43% (95% CI, 11% to 63%; P = .014). Two months post-immunization, geometric mean concentrations of serum GBS type III CPS-specific immunoglobulin G were 12.6 µg/mL (95% CI, 9.95 to 15.81) in GBS III-TT recipients, representing a 4-fold increase from baseline in 95% of women, which persisted. Both vaccines were well tolerated. Conclusions GBS CPS III-TT conjugate vaccine significantly delayed acquisition of vaginal and rectal GBS III colonization. In addition to its use for maternal immunization to passively protect infants with maternally derived antibodies, a multivalent vaccine might also serve to reduce fetal and neonatal exposure to GBS. Clinical Trials Registration NCT00128219.

Structural determination and serology of the native polysaccharide antigen of type-III group B Streptococcus

1980 ◽  
Vol 58 (2) ◽  
pp. 112-120 ◽  
Author(s):  
Harold J. Jennings ◽  
Karl-Gunnar Rosell ◽  
Dennis L. Kasper
Keyword(s):  
Sialic Acid ◽  
Group B Streptococcus ◽  
Rabbit Antiserum ◽  
Ph Control ◽  
Molar Ratio ◽  
Polysaccharide Antigen ◽  
Type Iii ◽  
Group B ◽  
Unit Formula ◽  
Ph Controlled

The native polysaccharide antigen isolated from type-III group B Streptococcus contains D-galactose (Gal), D-glucose (Glc), 2-acetamido-2-deoxy-D-glucose (GlcNAc), and sialic acid (NeuNAc) in the molar ratio of 2:1:1:1 and its structure can be represented by the following repeating unit:[Formula: see text]By cleavage of all the labile sialic acid end groups the incomplete type-III antigen is obtained which is structurally identical to the S. pneumoniae type-14 polysaccharide. Thus, the native type-III polysaccharide is serologically distinct from the incomplete type-III antigen by virtue of the former having determinants terminating in sialic acid and the latter in β-D-galactopyranose units. None of these latter determinants could be detected in streptococcal organisms grown under pH-controlled conditions (pH 7.0) or in rabbit antiserum made to these pH-controlled organisms. However, in antisera produced in rabbits to the same organisms grown without pH control (Lancefield procedures), antibodies to both types of determinant could be detected. This can be attributed to the removal of some of the masking sialic acid residues from the cell-associated native polysaccharide by degradative procedures which occur during these latter conditions.

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