Taxonomic group: bacteria / Firmicutes
(Phylum: Firmicutes)
Associated disease: infection due to Streptococcus pneumoniae [ICD11:
XN3PW 
]
NCBI PubMed ID: 30781826Publication DOI: 10.3390/ph12010028Journal NLM ID: 101238453Publisher: Basel, Switzerland: MDPI
Correspondence: mkuttel
cs.uct.ac.za; neil.ravenscroft
uct.ac.za
Institutions: Department of Computer Science, University of Cape Town, Cape Town 7701, South Africa, Department of Chemistry, University of Cape Town, Cape Town 7701, South Africa
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 βDGlc(1→6)βDGlcNAc 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.
conformation, serotype, Streptococcus, Streptococcus pneumoniae, capsular polysaccharide, group B Streptococcus, molecular modeling, conjugate vaccines, carbohydrate antigen
Structure type: polymer chemical repeating unit
Location inside paper: S. pneumoniae type 14 (Pn14 PS)
Compound class: CPS, O-polysaccharide, O-antigen
Contained glycoepitopes: IEDB_130646,IEDB_130697,IEDB_135813,IEDB_136044,IEDB_137340,IEDB_137472,IEDB_137776,IEDB_1391966,IEDB_1392542,IEDB_140108,IEDB_140110,IEDB_140122,IEDB_141794,IEDB_141807,IEDB_142351,IEDB_142487,IEDB_142488,IEDB_143634,IEDB_146664,IEDB_149138,IEDB_149139,IEDB_149141,IEDB_149142,IEDB_149143,IEDB_149144,IEDB_149145,IEDB_149147,IEDB_149148,IEDB_149149,IEDB_149150,IEDB_149151,IEDB_151531,IEDB_190606,IEDB_983931,SB_145,SB_165,SB_166,SB_173,SB_187,SB_192,SB_195,SB_30,SB_6,SB_7,SB_88
Methods: 13C NMR, 1H NMR, NMR-2D, conformation analysis, MD simulations, molecular modeling
Comments, role: published chemical repeating unit frame was shifted for the uniformity of structures in the database
3D data: molecular modeling
Related record ID(s): 1483
NCBI Taxonomy refs (TaxIDs): 1313Reference(s) to other database(s): GTC:G52755VD, GlycomeDB:
2039, CCSD:
11172, CBank-STR:12723
Show glycosyltransferases
There is only one chemically distinct structure:
Found 
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