Functional Antibodies to the O-Acetylated Pneumococcal Serotype 15B Capsular Polysaccharide Have Low Cross-Reactivities with Serotype 15C

Rajam, Gowrisankar; Carlone, George M.; Romero-Steiner, Sandra

doi:10.1128/cvi.00184-07

Cited by 33 publications

(25 citation statements)

References 24 publications

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“…Perhaps the most important unstable modification may be O-acetylation. Knowledge of O-acetylation is important because O-acetyl groups can contribute to the conformation of PS and are often antigenic targets (epitopes) (e.g., serotypes 15B/C, 11A, and others [44]). Yet, O-acetyl groups can be easily lost and variably expressed, and therefore it can be quite difficult to assign the location and degree of O-acetylation exactly.…”

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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Section: Biochemical Elucidation Of Capsular Diversitymentioning

confidence: 99%

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

et al. 2015

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“…Serotypes 1 and 5, which were the most resistant to C3 opsonization and opsonophagocytosis, have a smaller number of available targets (-OH or -NH 2 groups) for C3b to make ester or amide linkages. The importance of acetyl groups to the antigenicity of pneumococcal polysaccharides was reported in a previous study in which the functional activity of antibodies was evaluated using an opsonophagocytic assay (41). It was shown that the target of vaccine induced antibodies was linked to an Oacetyl group present in the monosaccharide residues of serotype 15B and that these antibodies were not cross-reactive against serotype 15C, whose capsular polysaccharide is otherwise identical but not acetylated (41).…”

Section: Vol 78 2010mentioning

confidence: 99%

Serotype-Related Variation in Susceptibility to Complement Deposition and Opsonophagocytosis among Clinical Isolates of Streptococcus pneumoniae

et al. 2010

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The polysaccharide capsule is a major virulence factor of Streptococcus pneumoniae; it affects complement resistance and shields the bacterium from phagocytes. Certain capsular serotypes appear to be better able to cause invasive disease than others. Serotypes 1 and 5 are common causes of invasive disease but are rarely isolated from healthy carriers, whereas serotypes 6B and 23F are more frequently isolated from carriage than invasive disease. We have recently shown that serotypes 6B and 19F differ in resistance to complement C3 deposition and opsonophagocytic killing. In this study we assessed the complement resistance and susceptibility to opsonophagocytosis of several other serotypes targeted by the pneumococcal conjugate vaccines. Clinical isolates of serotypes 1, 4, 5, 14, 18C, and 23F were tested along reference strains of corresponding capsular types. The concentration of anticapsular antibodies required for opsonophagocytic killing correlated inversely with C3 deposition on the serotype. Serotype 1 was the most resistant of the clinical isolates to C3 deposition and, along with serotypes 5 and 19F, required the highest concentration of capsule antibodies for opsonophagocytic killing, whereas serotype 23F was the most sensitive to opsonophagocytosis. Sensitivity to C3 deposition and opsonophagocytosis was associated with serotype-specific mortality of invasive pneumococcal disease, suggesting that the primary pathogens, such as serotypes 1 and 5, are more resistant to complement and require a higher concentration of capsule antibodies for opsonophagocytic killing than the opportunistic serotypes such as 6B and 23F, which are associated with a more severe disease outcome.

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“…One common variation is O-acetylation, which can alter both immune recognition and capsular physicochemical properties. Pneumococcal and meningococcal vaccine trials found that O-acetyl groups can be targets of vaccine-elicited antibodies and suggested that O-acetylation could be necessary for a successful vaccine response (8,9). O-acetylation is also important for innate immune recognition.…”

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confidence: 99%

Position of O-Acetylation within the Capsular Repeat Unit Impacts the Biological Properties of Pneumococcal Serotypes 33A and 33F

et al. 2017

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Streptococcus pneumoniae (pneumococcus) produces many capsule types that differ in their abilities to evade host immune recognition. To explain these serotypedependent protective capacities, many studies have investigated capsular thickness or the interaction of the capsule with complement proteins, but the effects of small chemical modifications of the capsule on its function have not been studied. One small chemical modification found frequently among pneumococcal capsules is O-acetylation. Pneumococcal serotype 33A has two membrane-bound O-acetyltransferase genes, wciG and wcjE. A 33A wcjE-deficient variant, 33F, occurs naturally and is increasing in prevalence in the wake of widespread conjugate vaccine use, but no wciG-deficient variants have been reported. To study the biological consequence of the loss of O-acetylation, we created wciG-deficient variants in both serotypes 33A and 33F, which we named 33X1 (ΔwciG) and 33X2 (ΔwciG ΔwcjE). Serotypes 33X1 and 33X2 express novel capsule types based on serological and biochemical analyses. We found that loss of WcjE-mediated O-acetylation appears not to affect cell wall shielding, since serotypes 33A and 33F exhibit comparable nonspecific opsonophagocytic killing, biofilm production, and adhesion to nasopharyngeal cells, though serotype 33F survived short-term drying better than serotype 33A. Loss of WciG-mediated O-acetylation in serotypes 33X1 and 33X2, however, resulted in a phenotype resembling that of nonencapsulated strains: increased cell wall accessibility, increased nonspecific opsonophagocytic killing, enhanced biofilm formation, and increased adhesion to nasopharyngeal cells. We conclude that WciG-mediated, but not WcjE-mediated, O-acetylation is important for producing protective capsules in 33A and that small chemical changes to the capsule can drastically affect its biological properties.KEYWORDS O-acetyltransferase, O-acetylation, capsular diversity, pneumococcal vaccine, capsular polysaccharide, serotype S treptococcus pneumoniae (pneumococcus) is an important human pathogen that can colonize the nasopharynx asymptomatically and disseminate opportunistically to cause pneumonia, meningitis, septicemia, and otitis media. The pneumococcus has a polysaccharide capsule, and 98 distinct capsular types (serotypes) have been identified based on chemical differences in their capsular repeat units (1-3). These chemical differences are mediated by genetic changes in the capsular polysaccharide synthesis (cps) operon (4) and result in different reactivities with anti-capsule antibodies. The capsule is essential for pneumococcal virulence (5), since it shelters pneumococci from complement fixation and opsonophagocytosis (6). However, differences in capsule type have been shown to affect complement fixation and virulence (7).

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Functional Antibodies to the O-Acetylated Pneumococcal Serotype 15B Capsular Polysaccharide Have Low Cross-Reactivities with Serotype 15C

Cited by 33 publications

References 24 publications

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

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

Serotype-Related Variation in Susceptibility to Complement Deposition and Opsonophagocytosis among Clinical Isolates of Streptococcus pneumoniae

Position of O-Acetylation within the Capsular Repeat Unit Impacts the Biological Properties of Pneumococcal Serotypes 33A and 33F

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