Characterization of the capsular antigen of Streptococcus pneumoniae serotype 35B

Beynon, Linda M.; Richards, James C.; Perry, Malcolm B.; Kniskern, Peter J.

doi:10.1139/v95-006

Cited by 6 publications

(10 citation statements)

References 21 publications

(13 reference statements)

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“…While this study 45 confirmed the previously established structure for the homologous CPS (Fig. 11A), 94 it also led to the identification of a novel S. pneumoniae serotype, named 35D by the authors. 96 S. pneumoniae type 35D is genetically very similar to serotype 35B, nevertheless the…”

Section: -96 40supporting

confidence: 86%

Bacterial polysaccharides as major surface antigens: interest in O-acetyl substitutions

Mulard¹

2017

Carbohydrate Chemistry

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Section: -96 40supporting

confidence: 86%

Bacterial polysaccharides as major surface antigens: interest in O-acetyl substitutions

Mulard¹

2017

Carbohydrate Chemistry

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“…(Table 3) for serotype 35B and 35D polysaccharides were achieved by twodimensional (2D) NMR experiments, as described in Materials and Methods. The chemical shifts are very similar to those described for serotype 35B polysaccharide and its O-deacetylated form (18). Although the spectra of serotypes 35B and 35D are largely Table 1.…”

Section: Resultssupporting

confidence: 67%

Discovery of Novel Pneumococcal Serotype 35D, a Natural WciG-Deficient Variant of Serotype 35B

2017

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Pneumococcus (Streptococcus pneumoniae) remains a significant cause of morbidity and mortality, especially among those at the extremes of age. Its capsular polysaccharide is essential for systemic virulence. Over 90 serologically distinct pneumococcal capsular polysaccharides (serotypes) are recognized, but they are unequal in prevalence. Because antibodies against the capsule are protective, polysaccharide conjugate vaccines, which are constructed against the most prevalent serotypes, have caused great reductions in pneumococcal disease caused by these serotypes. In response, however, the relative prevalences of serotypes have shifted. Certain previously rare serotypes, such as serotype 35B, are increasing in prevalence. Serotype 35B is thus a likely future vaccine candidate, but due to their previous rarity, serotype 35B strains have not been scrutinized for underlying heterogeneity. We studied putative serotype 35B clinical isolates to assess the uniformity of their serological reactions. While most isolates exhibited the accepted serology of serotype 35B, one isolate failed to bind to critical serotyping reagents. We determined that the genetic basis for this aberrant serology was the presence of inactivating mutations in the O-acetyltransferase gene wciG. Complementation studies in a wciG deletion strain verified that the mutant WciG was nonfunctional, and the serology of the mutant could be restored through complementation with a construct encoding a functional WciG. Nuclear magnetic resonance studies confirmed that the capsule of the WciG-deficient isolate lacked O-acetylation but was otherwise identical to serotype 35B. As this isolate expresses a unique serology with unique biochemistry and a stable genetic basis, we named its novel capsule serotype 35D.KEYWORDS O-acetylation, Streptococcus pneumoniae, capsular polysaccharide, serogroup 35, serotype 35B, serotype 35D S treptococcus pneumoniae (pneumococcus) is an important human pathogen that can express many different polysaccharide capsules that protect the organism from opsonophagocytic killing (1). As antibodies to the capsule are protective, currently available vaccines against pneumococcus are designed to elicit antibodies to the capsule and have been highly successful in reducing the incidence of invasive pneumococcal disease (IPD). A pneumococcal polysaccharide-protein conjugate vaccine (PCV) with polysaccharide from the seven most commonly observed serotypes (PCV7) was introduced in the United States in 2000 and reduced the incidence of IPD in children younger than 5 by over 75% (2); the updated 13-valent PCV (PCV13) has reduced the incidence of IPD by an additional 64% in this age group in the United States (3). However, the protection by these vaccines is serotype specific, and their widespread implementation has brought shifts in the serotypes found in both nasopharyngeal carriage and IPD (see, e.g., reference 4).

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“…The structures of S. pneumoniae CPS35F and CPS35C determined in the present study and those of CPS35A and CPS35B characterized previously (10,11) provide the first comprehensive description of serogroup 35 (Fig. 5).…”

Section: Discussionsupporting

confidence: 56%

“…Additional WcrH acceptors may thus be suggested from the structures of CPS36 and CPS43, the only serotypes in genetic cluster 4 (9) that remain to be structurally characterized. CR931721, CR931703, CR931704, CR931706, CR931715, CR931705, and CR931694) (A) with the corresponding CPS structures determined in the present or previous investigations (10,11,16,17,19) (B). The antigenic formulas of the CPS serotypes are indicated in parentheses.…”

Section: Discussionmentioning

confidence: 72%

“…Examples of crossreactions between these types include group 35 serum with types 42 and 47F (8), factor 34b serum with type 35F, factor 20b serum with type 35A, factor 29b serum with type 35B, and factor 20b and 42a sera with type 35C (9). Structures are available for many of these types (6), including CPS serotype 35A (CPS35A) (10) and CPS35B (11) but not for CPS35F and CPS35C. The absence of structures for the last two types limits description of the group, which was initially defined by cross-reactions of antiserum against S. pneumoniae serotype 35F with subsequently identified types (8,12).…”

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confidence: 99%

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Structures of Capsular Polysaccharide Serotypes 35F and 35C of Streptococcus pneumoniae Determined by Nuclear Magnetic Resonance and Their Relation to Other Cross-Reactive Serotypes

2015

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The structures of Streptococcus pneumoniae capsular polysaccharides (CPSs) are essential for defining the antigenic as well as genetic relationships between CPS serotypes. The four serotypes that comprise CPS serogroup 35 (i.e., types 35F, 35A, 35B, and 35C) are known to cross-react with genetically related type 20, 29, 34, 42, or 47F. While the structures of CPS serotype 35A (CPS35A) and CPS35B are known, those of CPS35F and CPS35C are not. In the present study, the serotypes of CPS35F and CPS35C were characterized by high-resolution heteronuclear magnetic resonance (NMR) spectroscopy and glycosyl composition analyses to reveal the following repeat unit structures:Glc␣1 where OAc indicates O-acetylated. Importantly, CPS35F, the immunizing serotype for the production of group 35 serum, more closely resembles CPS34 and CPS47F than other members of serogroup 35. Moreover, CPS35C is distinct from either CPS35F or CPS35B but closely related to CPS35A and identical to de-O-acetylated CPS42. The findings provide a comprehensive view of the structural and genetic relations that exist between the members of CPS serogroup 35 and other cross-reactive serotypes. T he virulence of Streptococcus pneumoniae depends in part on the production of capsular polysaccharides (CPSs) that protect invading bacteria from phagocytosis and subsequent killing by host neutrophils (1). When administered in vaccines, these polysaccharides elicit the formation of opsonic antibodies that confer serotype-specific protective immunity. Currently available CPS-based vaccines include the 23-valent polysaccharide vaccine and the 13-valent conjugate vaccine. The widespread use of these vaccines, while highly effective in preventing invasive pneumococcal disease, may also favor the emergence of nonvaccine, replacement serotypes (2) or possible new serotypes by recombination of existing strains (3). Surveillance of both vaccine and nonvaccine pneumococcal serotypes is thus essential for monitoring and maintaining vaccine efficacy. IMPORTANCE Cross-reactions of diagnostic rabbit antisera withTwenty-four of the 92 presently recognized CPS serotypes (4-6) are distinct in the Danish system of nomenclature, while the remaining 68 are distributed among 21 serogroups that contain from two to five members each. For the most part, cross-reactions between serotypes are limited to members of the same CPS serogroup. Exceptions do, however, occur, most notably among a group of nonvaccine serotypes (7) that includes the members of CPS serogroup 35 (i.e., 35F, 35A, 35B, and 35C) and other individual types (i.e., 20, 29, 34, 42, and 47F). Examples of crossreactions between these types include group 35 serum with types 42 and 47F (8), factor 34b serum with type 35F, factor 20b serum

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Characterization of the capsular antigen of Streptococcus pneumoniae serotype 35B

Cited by 6 publications

References 21 publications

Bacterial polysaccharides as major surface antigens: interest in O-acetyl substitutions

Bacterial polysaccharides as major surface antigens: interest in O-acetyl substitutions

Discovery of Novel Pneumococcal Serotype 35D, a Natural WciG-Deficient Variant of Serotype 35B

Structures of Capsular Polysaccharide Serotypes 35F and 35C of Streptococcus pneumoniae Determined by Nuclear Magnetic Resonance and Their Relation to Other Cross-Reactive Serotypes

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