Taxonomic group: bacteria / Firmicutes
(Phylum: Firmicutes)
NCBI PubMed ID: 32364376Publication DOI: 10.1021/acsinfecdis.0c00063Journal NLM ID: 101654580Publisher: Washington, DC: American Chemical Society
Correspondence: J. D. C. Codée <jcodee
chem.leidenuniv.nl>; N. E. Nifantiev <nen
ioc.ac.ru>; J. Huebner <johannes.huebner
med.uni-muenchen.de>
Institutions: N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia, Division of Paediatric Infectious Diseases, Dr. von Hauner Children's Hospital, Ludwig Maximilians University, Munich 80337, Germany, Bio-Organic Synthesis, Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands, Istituto di Microbiologia, Universita Cattolica del Sacro Cuore, Rome 00168, Italy, Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, Rome 00168, Italy
Infections caused by Enterococcus spp. are a major concern in the clinical setting. In Enterococcus faecalis, the capsular polysaccharide diheteroglycan (DHG), composed of β-d-galactofuranose-(1→3)-β-d-glucopyranose repeats, has been described as an important virulence factor and as a potential vaccine candidate against encapsulated strains. Synthetic structures emulating immunogenic polysaccharides present many advantages over native polysaccharides for vaccine development. In this work, we described the synthesis of a library of DHG oligomers, differing in length and order of the monosaccharide constituents. Using suitably protected thioglycoside building blocks, oligosaccharides up to 8-mer in length built up from either Galf-Glcp or Glcp-Galf dimers were generated, and we evaluated their immunoreactivity with antibodies raised against DHG. After the screening, we selected two octasaccharides, having either a galactofuranose or glucopyranose terminus, which were conjugated to a carrier protein for the production of polyclonal antibodies. The resulting antibodies were specific toward the synthetic structures and mediated in vitro opsonophagocytic killing of different encapsulated E. feacalis strains. The evaluated oligosaccharides are the first synthetic structures described to elicit antibodies that target encapsulated E. faecalis strains and are, therefore, promising candidates for the development of a well-defined enterococcal glycoconjugate vaccine.
capsular polysaccharide, vaccine, Enterococcus faecalis, diheteroglycan, opsonophagocytic assay, synthetic carbohydrate
Structure type: polymer chemical repeating unit
Location inside paper: abstract, Fig.1A
Compound class: CPS, cell wall polysaccharide
Contained glycoepitopes: IEDB_136095,IEDB_137472,IEDB_142488,IEDB_146664,IEDB_190606,IEDB_983931,SB_192
Methods: ELISA, chemical synthesis, biotinylation, opsonophagocytic assay, immunizations
Comments, role: Enterococcus faecalis type 2 serotype CPS-C
NCBI Taxonomy refs (TaxIDs): 1351
Show glycosyltransferases
There is only one chemically distinct structure:
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