%0 Journal Article
%T Conformation and Cross-Protection in Group B Streptococcus Serotype III and Streptococcus pneumoniae Serotype 14: A Molecular Modeling Study
%A Michelle M. Kuttel
%A Neil Ravenscroft
%J Archive of "Pharmaceuticals".
%D 2019
%R 10.3390/ph12010028
%X Although the branched capsular polysaccharides of Streptococcus agalactiae serotype III (GBSIII PS) and Streptococcus pneumoniae serotype 14 (Pn14 PS) differ only in the addition of a terminal sialic acid on the GBSIII PS side chains, these very similar polysaccharides are immunogenically distinct. Our simulations of GBSIII PS, Pn14 PS and the unbranched backbone polysaccharide provide a conformational rationale for the different antigenic epitopes identified for these PS. We find that side chains stabilize the proximal ¦ÂdGlc(1¡ú6) ¦ÂdGlcNAc backbone linkage, restricting rotation and creating a well-defined conformational epitope at the branch point. This agrees with the glycotope structure recognized by an anti-GBSIII PS functional monoclonal antibody. We find the same dominant solution conformation for GBSIII and Pn14 PS: aside from the branch point, the backbone is very flexible with a ¡°zig-zag¡± conformational habit, rather than the helix previously proposed for GBSIII PS. This suggests a common strategy for bacterial evasion of the host immune system: a flexible backbone that is less perceptible to the immune system, combined with conformationally-defined branch points presenting human-mimic epitopes. This work demonstrates how small structural features such as side chains can alter the conformation of a polysaccharide by restricting rotation around backbone linkages
%K capsular polysaccharide
%K carbohydrate antigen
%K molecular modeling
%K Group B Streptococcus
%K Streptococcus pneumoniae
%K conjugate vaccines
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469160/