Conformation and Cross-Protection in Group B Streptococcus Serotype III and <i>Streptococcus pneumoniae</i> Serotype 14: A Molecular Modeling Study
Although the branched capsular polysaccharides of <i>Streptococcus agalactiae</i> serotype III (GBSIII PS) and <i>Streptococcus pneumoniae</i> serotype 14 (Pn14 PS) differ only in the addition of a terminal sialic acid on the GBSIII PS side chains, these very similar polysacc...
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| Main Authors: | , |
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| Format: | Book |
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MDPI AG,
2019-02-01T00:00:00Z.
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| Summary: | Although the branched capsular polysaccharides of <i>Streptococcus agalactiae</i> serotype III (GBSIII PS) and <i>Streptococcus pneumoniae</i> 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 <inline-formula> <math display="inline"> <semantics> <mi>β</mi> </semantics> </math> </inline-formula><span style="font-variant: small-caps;">d</span>Glc(1→6)<inline-formula> <math display="inline"> <semantics> <mi>β</mi> </semantics> </math> </inline-formula><span style="font-variant: small-caps;">d</span>GlcNAc 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. |
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| Item Description: | 1424-8247 10.3390/ph12010028 |