Taxonomic group: bacteria / Firmicutes
(Phylum: Firmicutes)
Host organism: Homo sapiens
Associated disease: anthrax [ICD11:
1B97 
, ICD11:
XN94F ];
infection due to Bacillus anthracis [ICD11:
XN94F ]
Publication DOI: 10.3390/molecules23082079Journal NLM ID: 100964009Publisher: Basel, Switzerland: MDPI
Correspondence: roberto.x.adamo
gsk.com
Institutions: NIDDK, LBC, National Institutes of Health, Bethesda, MD 20892-0815, USA, GSK, Research Centre, via Fiorentina 1, 53100 Siena, Italy, Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
The tetrasaccharide (2-O-methyl-4-(3-hydroxy-3-methylbutamido)-4,6-dideoxy-α-D-glucopyranosyl-(1-3)-α-L-rhamnopyranosyl-(1-3)-α-L-rhamnopyranosyl-(1-2)-L-rhamnopyranose)from the major exosporium protein (BclA) of Bacillus anthracis has been proposed as a target for development of diagnostics and immune therapy or prophylaxis. While the immunodominant character of the anthrose residue has been previously elucidated, the role of the stereochemical configuration of the downstream rhamnose is unknown. Because the linkage of this residue to the GlcNAc bridging the glycan and the protein is lost during isolation of the tetrasaccharide, its alpha- and β-glycoforms have been synthesized. Herein, we prepared neoglycoconjugates from a series of fragments of the tetrasaccharide, including the complete alpha- and beta-tetrasaccharide glycoforms, a 2-demethoxylated version of the alpha-tetrasaccharide, and the alpha- and beta-trirhamnosides and CRM197. By immunization of mice, we showed that the anti alpha- and beta-tetrasaccharide serum equally recognized both glycoforms. In contrast the sera produced following immunization with the alpha- and beta-trirhamnoside fragments exhibited higher recognition for their own antigens than for their anomeric counterparts. The anti alpha- and beta-tetrasaccharide sera recognized Sterne spores in a comparable fashion. DBclA spores not expressing the major exosporium protein were also recognized by the same sera, while mutants that produced the carbohydrate antigen with deletion of either rhamnose or anthrose were not. The tetrasaccharide could, therefore, be expressed in proteins other than BlcA. This work proves that alpha- and beta-tetrasaccharide are equally potent immunogens.
carbohydrates, glycoconjugates, vaccines, Anthrose, Bacillus anthracis, B.anthracis, BclA, Diagnostics
Structure type: oligomer
Location inside paper: abstract, fig.1
Trivial name: anthrose tetrasaccharide
Contained glycoepitopes: IEDB_133754,IEDB_136105,IEDB_225177,IEDB_885823
Methods: ELISA, chemical synthesis, MALDI-TOF MS, serological methods, immunization, immunogenicity in mice, glycoconjugation
Biological activity: α- and β-glycoform of the tetrasaccharide could be used as antigen for immunoprophylaxis or immunotherapy against B. anthracis
NCBI Taxonomy refs (TaxIDs): 1392
Show glycosyltransferases
There is only one chemically distinct structure:
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