NMR structural analysis of the capsular polysaccharide from Streptococcus pneumoniae serotype 6C

Cai, Ping; Moran, Justin; Pavliak, Viliam; Deng, Cunbao; Khoury, Nancy; Marcq, Olivier; Ruppen, Mark E.

doi:10.1016/j.carres.2012.01.017

Cited by 14 publications

(9 citation statements)

References 14 publications

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“…Because the anomeric signals in the 1 H NMR spectra correspond to residues in PS RUs, we first compared the anomeric signals of 6X12 PS with those of 6A and 6C PSs. Three signals have been observed in the anomeric region of 6A (5.60, 5.10, and 5.02 ppm), corresponding to the anomeric protons of ␣Gal, ␣Glc, and Rha (26). Similarly, the one-dimensional 1 H spectrum of 6C has three signals (5.57, 5.10, and 5.02 ppm), which respectively correspond to the anomeric protons of ␣GlcЈ, ␣Glc, and Rha.…”

Section: Serologic Characterization Of Two Serogroup 6 Variants-tomentioning

confidence: 95%

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Discovery of Streptococcus pneumoniae Serotype 6 Variants with Glycosyltransferases Synthesizing Two Differing Repeating Units

Oliver

Linden

Küntzel

et al. 2013

Journal of Biological Chemistry

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Background: Two atypical serogroup 6 strains have been discovered. Results: They express capsular polysaccharide with two different repeating units and share A150T mutation in WciN␣. Conclusion: This mutation shifts WciN␣ from a galactosyltransferase to a bi-specific glycosyltransferase, creating two new hybrid serotypes: 6F and 6G. Significance: Pneumococci can change capsule serotypes by point mutations and may alter their interactions with the immunity of the host.

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Section: Serologic Characterization Of Two Serogroup 6 Variants-tomentioning

confidence: 95%

“…Signal assignments for 6A and 6C PS are described elsewhere and were used as a guide to assign 1 H and 13 C signals of 6X12 (26). As shown in Fig.…”

Section: Serologic Characterization Of Two Serogroup 6 Variants-tomentioning

confidence: 99%

Discovery of Streptococcus pneumoniae Serotype 6 Variants with Glycosyltransferases Synthesizing Two Differing Repeating Units

Oliver

Linden

Küntzel

et al. 2013

Journal of Biological Chemistry

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“…Development and advancement of analytical technologies, such as gas-liquid chromatography, nuclear magnetic resonance (NMR), and mass spectrometry (MS), have revolutionized structural studies of PS (28,31,34,35). Monosaccharide composition can be relatively easily determined with gas-liquid chromatography, and MS can provide information on the size of repeating units (34).…”

Section: Biochemical Elucidation Of Capsular Diversitymentioning

confidence: 99%

Pneumococcal Capsules and Their Types: Past, Present, and Future

et al. 2015

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SUMMARY Streptococcus pneumoniae (the pneumococcus) is an important human pathogen. Its virulence is largely due to its polysaccharide capsule, which shields it from the host immune system, and because of this, the capsule has been extensively studied. Studies of the capsule led to the identification of DNA as the genetic material, identification of many different capsular serotypes, and identification of the serotype-specific nature of protection by adaptive immunity. Recent studies have led to the determination of capsular polysaccharide structures for many serotypes using advanced analytical technologies, complete elucidation of genetic basis for the capsular types, and the development of highly effective pneumococcal conjugate vaccines. Conjugate vaccine use has altered the serotype distribution by either serotype replacement or switching, and this has increased the need to serotype pneumococci. Due to great advances in molecular technologies and our understanding of the pneumococcal genome, molecular approaches have become powerful tools to predict pneumococcal serotypes. In addition, more-precise and -efficient serotyping methods that directly detect polysaccharide structures are emerging. These improvements in our capabilities will greatly enhance future investigations of pneumococcal epidemiology and diseases and the biology of colonization and innate immunity to pneumococcal capsules.

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“…Data were analyzed with an ACD/NMR processor (Advanced Chemistry Development, Inc., Toronto, Canada). Chemical shifts were assigned based on published structures reported elsewhere (6,13).…”

Section: Methodsmentioning

confidence: 99%

“…Serotypes 6A and 6B encode WciN␣, which adds galactose to the repeat unit, whereas serotypes 6C and 6D encode WciN␤, which adds a second glucose (Glc=) (5,10,11). wciP allelism is the basis for differentiating serotypes 6A/6C from 6B/6D (6,12,13). WciP␣ links rhamnose to ribitol through an ␣(1-3) linkage, while WciP␤ mediates an ␣(1-4) linkage (6).…”

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confidence: 99%

Genetic, Biochemical, and Serological Characterization of a New Pneumococcal Serotype, 6H, and Generation of a Pneumococcal Strain Producing Three Different Capsular Repeat Units

Park

Geno

et al. 2015

Clin. Vaccine Immunol.

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dStreptococcus pneumoniae clinical isolates were recently described that produced capsular polysaccharide with properties of both serotypes 6A and 6B. Their hybrid serological property correlated with mutations affecting the glycosyltransferase WciP, which links rhamnose to ribitol by an ␣(1-3) linkage for serotypes 6A and 6C and an ␣(1-4) linkage for serotypes 6B and 6D. The isolates had mutations in the triad residues of WciP that have been correlated with enzyme specificity. The canonical triad residues of WciP are Ala192-Ser195-Arg254 for serotypes 6A and 6C and Ser192-Asn195-Gly254 for serotypes 6B and 6D. To prove that the mutations in the triad residues are responsible for the hybrid serotype, we introduced the previously described Ala192-Cys195-Arg254 triad into a 6A strain and found that the change made WciP bispecific, resulting in 6A and 6B repeat unit expression, although 6B repeat unit production was favored over production of 6A repeat units. Likewise, this triad permitted a 6C strain to express 6C and 6D repeat units. With reported bispecificity in WciN, which adds either glucose or galactose as the second sugar in the serogroup 6 repeat unit, the possibility exists for a strain to simultaneously produce all four serogroup 6 repeat units; however, when genes encoding both bispecific enzymes were introduced into a 6A strain, only 6A, 6B, and 6D repeat units were detected serologically. Nonetheless, this may be the first example of a bacterial polysaccharide with three different repeat units. This strategy of expressing multiple repeat units in a single polymer is a novel approach to broadening vaccine coverage by eliminating the need for multiple polysaccharide sources to cover multiple serogroup members. Streptococcus pneumoniae (pneumococcus) is a major human pathogen due to its being a leading cause of pneumonia, meningitis, otitis media, and sepsis. The capsular polysaccharide (PS) is an important virulence factor that protects pneumococci from the host innate immune response and greatly enhances their pathogenicity (1, 2). Over 90 capsular serotypes have been defined based on serological properties (3-8). In addition to unique serological properties, each serotype produces a capsular PS with a distinct biochemical structure and has a unique capsule biosynthesis locus (cps) that encodes the enzymes required for capsule synthesis (3). In most serotypes, these enzymes assemble the repeat units on the cytoplasmic leaflet of the membrane through stepwise addition of each sugar, export the completed repeat units to the outer leaflet, and polymerize the repeat units (9).Serogroup 6 contains four serotypes with unique repeat units-6A, 6B, 6C, and 6D-each with distinct serological, chemical, and genetic features (Fig. 1). The genetic basis for the four serotypes is the allelism of wciN and wciP. Serotypes 6A and 6B encode WciN␣, which adds galactose to the repeat unit, whereas serotypes 6C and 6D encode WciN␤, which adds a second glucose (Glc=) (5, 10, 11). wciP allelism is the basis for differentiatin...

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NMR structural analysis of the capsular polysaccharide from Streptococcus pneumoniae serotype 6C

Cited by 14 publications

References 14 publications

Discovery of Streptococcus pneumoniae Serotype 6 Variants with Glycosyltransferases Synthesizing Two Differing Repeating Units

Discovery of Streptococcus pneumoniae Serotype 6 Variants with Glycosyltransferases Synthesizing Two Differing Repeating Units

Pneumococcal Capsules and Their Types: Past, Present, and Future

Genetic, Biochemical, and Serological Characterization of a New Pneumococcal Serotype, 6H, and Generation of a Pneumococcal Strain Producing Three Different Capsular Repeat Units

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