Conformation and cross-protection in Group B Streptococcus serotype III and Streptococcus pneumoniae serotype 14: a molecular modeling study

Kuttel, Michelle M. and Ravenscroft, Neil (2019) Conformation and cross-protection in Group B Streptococcus serotype III and Streptococcus pneumoniae serotype 14: a molecular modeling study, Pharmaceuticals, 12, MDPI.

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Abstract

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 bDGlc(1->6)bDGlcNAc 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.

Item Type:	Journal article (online only)
Uncontrolled Keywords:	capsular polysaccharide; carbohydrate antigen; molecular modeling; Group B Streptococcus; Streptococcus pneumoniae; conjugate vaccines
Subjects:	Applied computing > Life and medical sciences
Date Deposited:	13 Mar 2019
Last Modified:	10 Oct 2019 15:31
URI:	http://pubs.cs.uct.ac.za/id/eprint/1306

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