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Taxonomic group: bacteria / Firmicutes (Phylum: Firmicutes)
Associated disease: infection due to Streptococcus pneumoniae [ICD11: XN3PW

]

NCBI PubMed ID: 32430472
Publication DOI: 10.1128/mBio.00937-20
Journal NLM ID: 101519231
Publisher: Washington, DC: American Society for Microbiology
Correspondence: mnahm

uabmc.edu
Institutions: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA, Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA, Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom, Parasites and Microbes, Wellcome Sanger Institute, Hinxton, Cambridge, United Kingdom, Cambodia Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia, Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom, Department of Ophthalmology, University of California, San Francisco, California, USA, Emory Global Health Institute, Emory University, Atlanta, Georgia, USA

Streptococcus pneumoniae (pneumococcus) is a major human pathogen producing structurally diverse capsular polysaccharides. Widespread use of highly successful pneumococcal conjugate vaccines (PCVs) targeting pneumococcal capsules has greatly reduced infections by the vaccine types but increased infections by nonvaccine serotypes. Herein, we report a new and the 100th capsule type, named serotype 10D, by determining its unique chemical structure and biosynthetic roles of all capsule synthesis locus (cps) genes. The name 10D reflects its serologic cross-reaction with serotype 10A and appearance of cross-opsonic antibodies in response to immunization with 10A polysaccharide in a 23-valent pneumococcal vaccine. Genetic analysis showed that 10D cps has three large regions syntenic to and highly homologous with cps loci from serotype 6C, serotype 39, and an oral streptococcus strain (S. mitis SK145). The 10D cps region syntenic to SK145 is about 6 kb and has a short gene fragment of wciNalpha at the 5' end. The presence of this nonfunctional wciNalpha fragment provides compelling evidence for a recent interspecies genetic transfer from oral streptococcus to pneumococcus. Since oral streptococci have a large repertoire of cps loci, widespread PCV usage could facilitate the appearance of novel serotypes through interspecies recombination.IMPORTANCE The polysaccharide capsule is essential for the pathogenicity of pneumococcus, which is responsible for millions of deaths worldwide each year. Currently available pneumococcal vaccines are designed to elicit antibodies to the capsule polysaccharides of the pneumococcal isolates commonly causing diseases, and the antibodies provide protection only against the pneumococcus expressing the vaccine-targeted capsules. Since pneumococci can produce different capsule polysaccharides and therefore reduce vaccine effectiveness, it is important to track the appearance of novel pneumococcal capsule types and how these new capsules are created. Herein, we describe a new and the 100th pneumococcal capsule type with unique chemical and serological properties. The capsule type was named 10D for its serologic similarity to 10A. Genetic studies provide strong evidence that pneumococcus created 10D capsule polysaccharide by capturing a large genetic fragment from an oral streptococcus. Such interspecies genetic exchanges could greatly increase diversity of pneumococcal capsules and complicate serotype shifts.

Streptococcus pneumoniae, capsule, vaccine, genetic exchange

Structure type: polymer chemical repeating unit
Location inside paper: Fig.4, table 4
Compound class: CPS
Contained glycoepitopes: IEDB_114703,IEDB_130648,IEDB_136044,IEDB_136095,IEDB_136906,IEDB_137472,IEDB_137473,IEDB_141794,IEDB_151528,IEDB_190606,IEDB_591403,SB_165,SB_166,SB_187,SB_195,SB_21,SB_7,SB_88

Methods: 13C NMR, 1H NMR, NMR-2D, ELISA, serological methods, genetic methods, bioinformatic analysis, opsonophagocytosis assay
Biosynthesis and genetic data: wciB, wcjH, wcrG,wcrD,wcyO, wciF, wcrC, whal
Comments, role: published polymerization frame was shifted for conformity with other records.

Related record ID(s): 3661, 3662, 32102
NCBI Taxonomy refs (TaxIDs): 1313
Reference(s) to other database(s): GTC:G96867FB
Show glycosyltransferases

There is only one chemically distinct structure:

*OC[C@@H](O)[C@@H]1O[C@@H](O[C@H]2[C@@H](O)[C@@H](CO)O[C@@H](O[C@H]3[C@@H](CO[C@@H]4O[C@H](CO)[C@H](O)[C@H](O)[C@H]4O)O[C@@H](O[C@H]4[C@@H](O)[C@@H](CO)O[C@H](OC[C@H](O)[C@H](O)[C@H](O)COP(*)(=O)O)[C@@H]4O)[C@H](NC(C)=O)[C@H]3O[C@@H]3O[C@@H]([C@H](O)COC(C)=O)[C@H](OC(C)=O)[C@H]3O)[C@@H]2O)[C@H](O)[C@H]1O

SVG MW SMILES 3D mol Ionize