Modeling of pneumococcal serogroup 10 capsular polysaccharide molecular conformations provides insight into epitopes and observed cross-reactivity

Richardson, Nicole I; Kuttel, Michelle M.; Ravenscroft, Neil

doi:10.3389/fmolb.2022.961532

Cited by 4 publications

(9 citation statements)

References 63 publications

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“…The determination of the glycosidic linkages was achieved by GLC-MS analysis of the partially methylated alditol acetates which identified: 4,5-Rib-ol, 3-Glc p , 4-Gal p or 5-Gal f , 3-Gal p , and 3-GalNAc p in the molar ratio of 0.4:1.6:2.1:1.0:0.7. These data are consistent with a linear hexasaccharide repeat unit without branch points and side chains, unlike the repeat units reported for related serotypes 10B ( 42 ) and 33B ( 43 ).…”

Section: Resultssupporting

confidence: 87%

Streptococcus pneumoniae serotype 33G: genetic, serological, and structural analysis of a new capsule type

Manna,

Werren,

Ortika

et al. 2024

Microbiol Spectr

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Streptococcus pneumoniae (the pneumococcus) is a human pathogen responsible for a spectrum of diseases such as pneumonia, sepsis, and meningitis. The capsule is the major pneumococcal virulence factor and is encoded by the capsular polysaccharide ( cps ) locus, a recombination hotspot that has resulted in over 100 distinct capsular polysaccharide types (serotypes) identified to date. Recently, 33X (also known as 10X) was proposed as a putative novel serotype, but the capsule structure had not been elucidated. Here, we provide an in-depth investigation of 33X, demonstrating it is a new pneumococcal capsular serotype. In this study, we screened 12,850 nasopharyngeal swabs from both healthy children and pneumonia patients (adults and children) in Mongolia collected between 2015 and 2022. We identified 20 pneumococcal 33X isolates. Using whole genome sequencing, we found that the 33X cps locus is a chimera of genes from pneumococcal serogroups 35, 10, and 33, as well as other Streptococcal species. Serotyping of 33X pneumococci by the Quellung reaction revealed a unique serological profile, typing as both 10B and 33B. Competitive ELISAs confirmed that antibodies that were generated in mice directed against 33X were inhibited by 33X pneumococci but not 10B or 33B. Lastly, the elucidation of the 33X capsule structure revealed that the polysaccharide is distinct from other serotypes, consisting of an O-acetylated hexasaccharide repeat unit of →5)-β-Gal f -(1→3)-β-Glc p -(1→5)-β-Gal f 2Ac-(1→3)-β-Gal p NAc-(1→3)-α-Gal p -(1→4)-Rib-ol-(5→P→. Therefore, 33X meets the requisite genetic, serological, and biochemical criteria to be designated as a new serotype, which we have named 33G. IMPORTANCE Streptococcus pneumoniae (the pneumococcus) is a bacterial pathogen with the greatest burden of disease in Asia and Africa. The pneumococcal capsular polysaccharide has biological relevance as a major virulence factor as well as public health importance as it is the target for currently licensed vaccines. These vaccines have limited valency, covering up to 23 of the >100 known capsular types (serotypes) with higher valency vaccines in development. Here, we have characterized a new pneumococcal serotype, which we have named 33G. We detected serotype 33G in nasopharyngeal swabs ( n = 20) from children and adults hospitalized with pneumonia, as well as healthy children in Mongolia. We show that the genetic, serological, and biochemical properties of 33G differ from existing serotypes, satisfying the criteria to be designated as a new serotype. Future studies should focus on the geographical distribution of 33G and any changes in prevalence following vaccine introduction.

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Section: Resultssupporting

confidence: 87%

Streptococcus pneumoniae serotype 33G: genetic, serological, and structural analysis of a new capsule type

Manna,

Werren,

Ortika

et al. 2024

Microbiol Spectr

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“…Determination of the glycosidic linkages was achieved by GLC-MS analysis of the partially methylated alditol acetates which identified: 4,5-Rib-ol, 3-Glc p , 4-Gal p or 5-Gal f , 3-Gal p , and 3-GalNAc p in the molar ratio of 0.4:1.6:2.1:1.0:0.7. These data are consistent with a linear hexasaccharide repeat unit without branch points and side chains, unlike the repeat units reported for related serotypes 10B (39) and 33B (40).…”

Section: Resultssupporting

confidence: 87%

“…Like 33B, 33G and other serotypes in serogroup 33 (33C and 33D) also possess a hexasaccharide backbone containing ribitol-5-P. In addition, 33G has an O-acetylated β-Gal f residue, found in all members of serogroup 33 and lacking in serogroup 10 capsules (39, 40). The presence of O-acetyl groups in the 33G capsule is likely to have important biological relevance given that O-acetylation impacts the structure of the polysaccharide, and is an epitope in pneumococcal capsules readily recognised by the immune system (44, 49).…”

Section: Discussionmentioning

confidence: 99%

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Streptococcus pneumoniaeserotype 33G: genetic, serological, and structural analysis of a new capsule type

Manna,

Werren,

Ortika

et al. 2023

Preprint

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Streptococcus pneumoniae(the pneumococcus) is a human pathogen responsible for a spectrum of diseases such as pneumonia, sepsis, and meningitis. The capsule is the major pneumococcal virulence factor and is encoded by the capsular polysaccharide (cps) locus, a recombination hot spot that has resulted in over 100 distinct capsular polysaccharide types (serotypes) identified to date. Recently, 33X (also known as 10X) was proposed as a putative novel serotype, but the capsule structure had not been elucidated. Here, we provide an in-depth investigation of 33X, demonstrating it is a new pneumococcal capsular serotype. In this study, we screened 12,850 nasopharyngeal swabs from both healthy children and pneumonia patients (adults and children) in Mongolia collected between 2015-2022. We identified 20 pneumococcal 33X isolates. Using whole genome sequencing, we found that the 33Xcpslocus is a chimera of genes from pneumococcal serogroups 35, 10 and 33, as well as other Streptococcal species. Serotyping of 33X pneumococci by the Quellung reaction revealed a unique serological profile, typing as both 10B and 33B. Competitive ELISAs confirmed that antibodies that were generated in mice directed against 33X were inhibited by 33X pneumococci but not 10B or 33B. Lastly, elucidation of the 33X capsule structure revealed that the polysaccharide is distinct from other serotypes, consisting of an O-acetylated hexasaccharide repeat unit of →5)-β-Galf-(1→3)-β-Glcp-(1→5)-β-Galf2Ac-(1→3)-β-GalpNAc-(1→3)-α-Galp-(1→4)-Rib-ol-(5→P→. Therefore, 33X meets the requisite genetic, serological, and biochemical criteria to be designated as a new serotype, which we have named 33G.IMPORTANCEStreptococcus pneumoniae(the pneumococcus) is a bacterial pathogen with the greatest burden of disease in Asia and Africa. The pneumococcal capsular polysaccharide has biological relevance as a major virulence factor, as well as public health importance as it is the target for currently licensed vaccines. These vaccines have limited valency, covering up to 23 of the >100 known capsular types (serotypes) with higher valency vaccines in development. Here, we have characterized a new pneumococcal serotype, which we have named 33G. We detected serotype 33G in nasopharyngeal swabs (n=20) from children and adults hospitalized with pneumonia, as well as healthy children in Mongolia. We show that the genetic, serological, and biochemical properties of 33G differs from existing serotypes, satisfying the criteria to be designated as a new serotype. Future studies should focus on the geographical distribution of 33G and any changes in prevalence following vaccine introduction.

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“…Cross-reactivity between serotypes Spn-10A, Spn-10B, Spn-10C and Spn-10F is complex with unclear structural reasons, serotype-specific rabbit antisera generated against a serotype recognized other serotypes, albeit with less affinity [ 67 ]. Ravenscroft and Kuttel recently published a molecular modeling study that together with relevant serological studies supports the inclusion of serotype 10A in a vaccine to best protect against serotypes 10 disease [ 68 ].…”

Section: Inconsistent Vaccine Efficacymentioning

confidence: 99%

Strengths and weaknesses of pneumococcal conjugate vaccines

et al. 2023

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Multivalent vaccines addressing an increasing number of Streptococcus pneumoniae types (7-, 10-, 13-, 15-, 20-valent) have been licensed over the last 22 years. The use of polysaccharide-protein conjugate vaccines has been pivotal in reducing the incidence of invasive pneumococcal disease despite the emergence of non-vaccine serotypes. Notwithstanding its undoubtable success, some weaknesses have called for continuous improvement of pneumococcal vaccination. For instance, despite their inclusion in pneumococcal conjugate vaccines, there are challenges associated with some serotypes. In particular, Streptococcus pneumoniae type 3 remains a major cause of invasive pneumococcal disease in several countries.Here a deep revision of the strengths and weaknesses of the licensed pneumococcal conjugate vaccines and other vaccine candidates currently in clinical development is reported.

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Modeling of pneumococcal serogroup 10 capsular polysaccharide molecular conformations provides insight into epitopes and observed cross-reactivity

Cited by 4 publications

References 63 publications

Streptococcus pneumoniae serotype 33G: genetic, serological, and structural analysis of a new capsule type

Streptococcus pneumoniae serotype 33G: genetic, serological, and structural analysis of a new capsule type

Streptococcus pneumoniaeserotype 33G: genetic, serological, and structural analysis of a new capsule type

Strengths and weaknesses of pneumococcal conjugate vaccines

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