Polysaccharide Capsule Composition of Pneumococcal Serotype 19A Subtypes Is Unaltered among Subtypes and Independent of the Nutritional Environment

Brugger, Silvio D.; Troxler, Lukas J.; Rüfenacht, Susanne; Frey, Pascal M.; Morand, Brigitte; Geyer, Rudolf; Mühlemann, Kathrin; Höck, Stefan; Thormann, Wolfgang; Furrer, Julien; Christen, Stephan; Hilty, Markus

doi:10.1128/iai.00474-16

Cited by 13 publications

(15 citation statements)

References 49 publications

(52 reference statements)

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“…The extraction and NMR analysis of capsular polysaccharide of types 23B and 23B1 were conducted as described previously ( Brugger etal. 2016 ; Hathaway etal.…”

Section: Methodsmentioning

confidence: 99%

Pneumococcal 23B Molecular Subtype Identified Using Whole Genome Sequencing

Kapatai¹,

Sheppard²,

Troxler³

et al. 2017

Genome Biology and Evolution

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The polysaccharide capsule is a major virulence factor of Streptococcus pneumoniae and the target of all currently licensed pneumococcal vaccines. At present, there are 92 serologically distinct pneumococcal serotypes. Structural and antigenic variation of capsular types is the result of genetic variation within the capsular polysaccharide synthesis (CPS) locus; however, genetic variation may not always result in phenotypic differences which produce novel serotypes. With the introduction of high throughput whole genome sequencing, discovery of novel genotypic variants is not unexpected and this study describes a novel variant of the serotype 23B CPS operon. This novel variant was characterized as a novel genotypic subtype (23B1) with ∼70% homology to the published 23B CPS sequence. High sequence variability was determined in eight cps genes involved in sugar biosynthesis. However, there was no distinction between the classic 23B serotype and 23B1 serologically or in terms of polysaccharide structure. Phylogenetic and eBURST analysis revealed a distinct lineage for 23B1 with multiple clones (UK, Thailand, and USA) that arose at different points during pneumococcal evolution. Analysis of the UK S. pneumoniae isolates (n = 121) revealed an upsurge of 23B1 ST2372 in 2011, after which this previously unseen ST increased to reach 50% proportion of the 23B sequenced isolates from 2013 and remained prevalent within our sequenced isolates from later years. Therefore, although the 23B1 variant appears to have no phenotypic impact and cannot be considered as novel serotype, it appears to have led to a genetic restructuring of the UK serotype 23B population.

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“…The extraction and NMR analysis of capsular polysaccharide of types 23B and 23B1 were conducted as described previously ( Brugger etal. 2016 ; Hathaway etal.…”

Section: Methodsmentioning

confidence: 99%

Pneumococcal 23B Molecular Subtype Identified Using Whole Genome Sequencing

Kapatai¹,

Sheppard²,

Troxler³

et al. 2017

Genome Biology and Evolution

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“…For over a century, S. pneumoniae has been categorized by serology with distinct serotypes identified on the basis of the greater than 90 immunologically and chemically distinct polysaccharide capsules that surround and protect the bacteria from phagocytosis (26). The capsular polysaccharide is also the basis of the current pneumococcal vaccines.…”

Section: Trafficking Of Pneumococci Through the Respiratory Tractmentioning

confidence: 99%

Streptococcus pneumoniae: Invasion and Inflammation

2019

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Streptococcus pneumoniae (the pneumoccus) is the leading cause of otitis media, community-acquired pneumonia, and bacterial meningitis. The success of the pneumococcus stems from its ability to persist in the population as a commensal and avoid killing by immune system. This chapter first reviews the molecular mechanisms that allow the pneumococcus to colonize and spread from one anatomical site to the next. Then, it discusses the mechanisms of inflammation and cytotoxicity during emerging and classical pneumococcal infections.

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“…For the more detailed analyses, strains 106.66 (serotype 6B) and 208.41 (serotype 7F) were chosen as examples of serotypes more commonly associated with commensal colonization of the nasopharynx and invasive disease, respectively, as well as representing one strain with a thick polysaccharide capsule and one with a thin capsule (Table 1). Bacteria were cultured as described previously (36). Briefly, bacteria were streaked out on CSBA plates and grown for ∼10 h at 37 °C in a 5% CO 2 atmosphere.…”

Section: Methodsmentioning

confidence: 99%

Carbon source regulates polysaccharide capsule biosynthesis in Streptococcus pneumoniae

Troxler

Werren

Schaffner

et al. 2019

Journal of Biological Chemistry

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The exopolysaccharide capsule of Streptococcus pneumoniae is an important virulence factor, but the mechanisms that regulate capsule thickness are not fully understood. Here, we investigated the effects of various exogenously supplied carbohydrates on capsule production and gene expression in several pneumococcal serotypes. Microscopy analyses indicated a near absence of the capsular polysaccharide (CPS) when S. pneumoniae was grown on fructose. Moreover, serotype 7F pneumococci produced much less CPS than strains of other serotypes (6B, 6C, 9V, 15, and 23F) when grown on glucose or sucrose. RNA-sequencing revealed carbon source-dependent regulation of distinct genes of WT strains and capsule-switch mutants of serotypes 6B and 7F, but could not explain the mechanism of capsule thickness regulation. In contrast, 31P NMR of whole-cell extract from capsule-knockout strains (Δcps) clearly revealed the accumulation or absence of capsule precursor metabolites when cells were grown on glucose or fructose, respectively. This finding suggests that fructose uptake mainly results in intracellular fructose 1-phosphate, which is not converted to CPS precursors. In addition, serotype 7F strains accumulated more precursors than did 6B strains, indicating less efficient conversion of precursor metabolites into the CPS in 7F, in line with its thinner capsule. Finally, isotopologue sucrose labeling and NMR analyses revealed that the uptake of the labeled fructose subunit into the capsule is <10% that of glucose. Our findings on the effects of carbon sources on CPS production in different S. pneumoniae serotypes may contribute to a better understanding of pneumococcal diseases and could inform future therapeutic approaches.

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Polysaccharide Capsule Composition of Pneumococcal Serotype 19A Subtypes Is Unaltered among Subtypes and Independent of the Nutritional Environment

Cited by 13 publications

References 49 publications

Pneumococcal 23B Molecular Subtype Identified Using Whole Genome Sequencing

Pneumococcal 23B Molecular Subtype Identified Using Whole Genome Sequencing

Streptococcus pneumoniae: Invasion and Inflammation

Carbon source regulates polysaccharide capsule biosynthesis in Streptococcus pneumoniae

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