Discovery and Characterization of Pneumococcal Serogroup 36 Capsule Subtypes, Serotypes 36A and 36B

Feroze A Ganaie, Jamil S Saad, Stephanie W Lo, Lesley McGee, Stephen D Bentley, Andries J van Tonder, Paulina Hawkins, Jeremy D Keenan, Juan J Calix, Moon H Nahm

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7 Citations (SciVal)

Abstract

Streptococcus pneumoniae can produce a wide breadth of antigenically diverse capsule types, a fact that poses a looming threat to the success of vaccines that target pneumococcal polysaccharide (PS) capsule. Yet, many pneumococcal capsule types remain undiscovered and/or uncharacterized. Prior sequence analysis of pneumococcal capsule synthesis (cps) loci suggested the existence of capsule subtypes among isolates identified as "serotype 36" according to conventional capsule typing methods. We discovered these subtypes represent two antigenically similar but distinguishable pneumococcal capsule serotypes, 36A and 36B. Biochemical analysis of their capsule PS structure reveals that both have the shared repeat unit backbone [→5)-α-d-Galf-(1→1)-d-Rib-ol-(5→P→6)-β-d-ManpNAc-(1→4)-β-d-Glcp-(1→] with two branching structures. Both serotypes have a β-d-Galp branch to Ribitol. Serotypes 36A and 36B differ by the presence of a α-d-Glcp-(1→3)-β-d-ManpNAc or α-d-Galp-(1→3)-β-d-ManpNAc branch, respectively. Comparison of the phylogenetically distant serogroup 9 and 36 cps loci, which all encode this distinguishing glycosidic bond, revealed that the incorporation of Glcp (in types 9N and 36A) versus Galp (in types 9A, 9V, 9L, and 36B) is associated with the identity of four amino acids in the cps-encoded glycosyltransferase WcjA. Identifying functional determinants of cps-encoded enzymes and their impact on capsule PS structure is key to improving the resolution and reliability of sequencing-based capsule typing methods and discovering novel capsule variants indistinguishable by conventional serotyping methods.

Original languageEnglish
Article numbere0002423
Number of pages11
JournalJournal of Clinical Microbiology
Volume61
Issue number4
Early online date27 Mar 2023
DOIs
Publication statusPublished - 20 Apr 2023

Bibliographical note

Funding Information:
We thank Rama Kandasamy and Andrew Pollard for providing the Nepalese isolate. This work was supported by the Global Pneumococcal Sequencing project funded by the Bill and Melinda Gates Foundation (grant code OPP1034556). The High-Field NMR facility at the University of Alabama at Birmingham was established through the NIH (1S10RR026478) and is supported by the UAB Comprehensive Cancer Center (NCI grant P30 CA013148). J.J.C. is supported by an NIH grant (K08 AI148582). The NMR facility at the Complex Carbohydrate Research Center, University of Georgia is supported by the Chemical Sciences, Geosciences and Biosciences Division, Office of Basic Energy Sciences, U.S. Department of Energy (grant no. DE-SC0015662 to Parastoo Azadi). UAB has Intellectual Property rights on some reagents used in the study. F.A.G., J.S.S., J.J.C., and M.H.N. are UAB employees. We declare that they have no other relevant conflicts of interest. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Keywords

  • Humans
  • Streptococcus pneumoniae
  • Serogroup
  • Reproducibility of Results
  • Serotyping
  • Polysaccharides
  • Pneumococcal Vaccines
  • Bacterial Capsules/chemistry
  • Pneumococcal Infections
  • cps locus typing
  • capsule polysaccharide
  • serotype

ASJC Scopus subject areas

  • Microbiology (medical)

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