Research

Structural, genetic, and serological elucidation of Streptococcus pneumoniae serogroup 24 serotypes: Discovery of a new serotype, 24C, with a variable capsule structure

Read the article

Abstract

Pneumococcal capsules are important in pneumococcal pathogenesis and vaccine development. Though conjugate vaccines have brought about a significant reduction in invasive pneumococcal disease (IPD) caused by vaccine serotypes, the relative serotype prevalence has shifted with dramatic emergence of serotype 24F in some countries. Herein, we describe fourteen isolates (thirteen IPD and one non-IPD) expressing a new capsule type, 24C, which resembles 24F but has a novel serological profile. We also describe the antigenic, biochemical, and genetic bases of 24F and 24C and the related serotypes 24A and 24B. Structural studies show that 24B, 24C, and 24F have identical polysaccharide backbones [β-Ribf-(1→4)-α-Rhap-(1→3)-β-GlcpNAc-(1→4)-β-Rhap-(1→4)-β-Glcp] but with different side chains: 24F has arabinitol-phosphate, and 24B has ribitol-phosphate. 24C has a mixture of 24F and 24B repeating units, with ratio of ribitol to arabinitol being strain-dependent. In contrast, 24A capsule has a backbone without β-Ribf but with arabinitol-phosphate and phosphocholine side chains. These structures indicate that factor-sera 24d and 24e respectively recognize arabinitol and ribitol, which explains the serology of serogroup 24, including those of 24C. The structures can be genetically described by the bi-specificity of wcxG, capable of transferring arabinitol or ribitol when arabinitol is limiting. Arabinitol is likely not produced in 24B but is produced in reduced amounts in 24C due to various mutations in abpA or abpB genes. Our findings demonstrate how pneumococci modulate their capsule structure and immunologic properties with small genetic changes, thereby evading host immune responses. Our findings also suggest a potential for new capsule types within serogroup 24.