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Open AccessArticle

Conformation and Cross-Protection in Group B Streptococcus Serotype III and Streptococcus pneumoniae Serotype 14: A Molecular Modeling Study

1
Department of Computer Science, University of Cape Town, Cape Town 7701, South Africa
2
Department of Chemistry, University of Cape Town, Cape Town 7701, South Africa
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2019, 12(1), 28; https://doi.org/10.3390/ph12010028
Received: 19 January 2019 / Revised: 1 February 2019 / Accepted: 9 February 2019 / Published: 13 February 2019
(This article belongs to the Special Issue Carbohydrates 2018)
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 β dGlc(1→6) β dGlcNAc 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. View Full-Text
Keywords: capsular polysaccharide; carbohydrate antigen; molecular modeling; Group B Streptococcus; Streptococcus pneumoniae; conjugate vaccines capsular polysaccharide; carbohydrate antigen; molecular modeling; Group B Streptococcus; Streptococcus pneumoniae; conjugate vaccines
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MDPI and ACS Style

Kuttel, M.M.; Ravenscroft, N. Conformation and Cross-Protection in Group B Streptococcus Serotype III and Streptococcus pneumoniae Serotype 14: A Molecular Modeling Study. Pharmaceuticals 2019, 12, 28. https://doi.org/10.3390/ph12010028

AMA Style

Kuttel MM, Ravenscroft N. Conformation and Cross-Protection in Group B Streptococcus Serotype III and Streptococcus pneumoniae Serotype 14: A Molecular Modeling Study. Pharmaceuticals. 2019; 12(1):28. https://doi.org/10.3390/ph12010028

Chicago/Turabian Style

Kuttel, Michelle M.; Ravenscroft, Neil. 2019. "Conformation and Cross-Protection in Group B Streptococcus Serotype III and Streptococcus pneumoniae Serotype 14: A Molecular Modeling Study" Pharmaceuticals 12, no. 1: 28. https://doi.org/10.3390/ph12010028

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