Comparative Molecular Modelling of Capsular Polysaccharide Conformations in Streptococcus suis Serotypes 1, 2, 1/2 and 14 Identifies Common Epitopes for Antibody Binding.

Michelle M Kuttel

doi:10.3389/fmolb.2022.830854

Abstract

Streptococcus suis is an encapsulated, commensal, potentially pathogenic bacterium that infects swine globally and causes sporadic life-threatening zoonotic septicemia and meningitis infections in humans. The capsular polysaccharide is a primary virulence factor for S. suis. As S. suis serotype 2 is the most prevalent serotype globally, the serotype 2 CPS is the primary target of current efforts to develop an effective glycoconjugate veterinary vaccine against S. suis. Possible cross-protection with related serotypes would broaden the coverage of a vaccine. The CPS in serotypes 2 and 1/2 differ at a single residue (Gal versus GalNAc), and both are similar to serotypes 1 and 14: all contain a terminal sialic acid on a side chain. However, despite this similarity, there is complex pattern of cross-protection for these serotypes, with varying estimations of the importance of sialic acid in a protective epitope. Further, a pentasaccharide without the terminal sialic acid has been identified as minimal epitope for serotype 2. Here we use molecular simulation to model the molecule conformations of the CPS in serotypes 2, 1/2, 1 and 14, as well as three vaccine candidate oligosaccharides. The common epitopes we identify assist in rationalizing the apparently contradictory immunological data and provide a basis for rational design of S. suis vaccines in the future.

Highlights

Streptococcus suis is an encapsulated, commensal, potentially pathogenic bacterium that primarily inhabits the upper respiratory tract of pigs
We focus on a characterization of the side chain conformations in each capsular polysaccharide (CPS), which are compared to the conformations of the Ss2 antigens frag3, frag4 and frag5
Because a well-defined helical conformation (Figures 3A,B), with side chains arranged on the outer edge, shields the backbone residues from solvent exposure, we find that the CPS backbone is an unlikely source of antibody epitopes for Ss2 and Ss1/2

Summary

Introduction

Streptococcus suis is an encapsulated, commensal, potentially pathogenic bacterium that primarily inhabits the upper respiratory tract of pigs. S. suis is a principal cause of death in piglets (Gottschalk 2011), with consequent economic losses to the swine industry, but is responsible for sporadic zoonotic meningitis, septicemia and other infections in humans who have been in contact with pigs, or consumed raw pork products (Goyette-Desjardins et al, 2014). Recent deadly outbreaks of infections in Asia mean that S. suis is considered to be a serious emerging zoonotic agent (Dutkiewicz et al, 2018). Development of effective treatments against S. suis is increasingly necessary, most a veterinary vaccine to limit disease in swine and transmission to humans (Segura 2015; Segura et al, 2016). Vaccination reduces the consumption of antibiotics and the development of antimicrobial resistance.

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Conclusion