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Campylobacter jejuni infection is now the main cause of diarrhea-related illnesses in humans. An efficacious vaccine for the traveler and developing world market would be welcomed. We are engaged in the discovery and characterization of serotype-specific C. jejuni capsule polysaccharides (CPSs) to study their role in virulence and as protective vaccine antigens. Our prototype conjugate vaccine with serotype HS23 CPS (strain 81-176) has been shown to fully protect non-human primates against diarrhea inflicted by C. jejuni HS23, but ultimately, a useful CPS-based vaccine will have to be multivalent. To this end, we describe here the creation of a CPS-conjugate vaccine against C. jejuni serotype HS15. Structural analysis revealed that a repeating block consisting of l-α-arabinofuranose (Ara) and 6-deoxy-l-α-gulo-heptopyranose (6d-gulo-Hep) comprised the CPS of serotype HS15 type strain ATCC 43442 [→3)-α-L-Araf-(1→3)-6d-l-α-gulo-Hepp(1→](n). Strategically, the non-reducing end of the CPS was activated and used in the attachment of CPS to CRM(197) to yield a conjugate vaccine. A serological assessment of the CPS(HS15)-CRM(197) conjugate with an anti-HS15 polyclonal antibody confirmed the conservation of antigenic epitopes, and subsequent inoculation of mice with CPS(HS15)-CRM(197) revealed that this conjugate was indeed capable of raising anti-CPS(HS15) antibodies.

Campylobacter jejuni, capsule polysaccharide, conjugate vaccine, Diarrheal vaccine, 6-deoxy-gulo-heptose

NCBI PubMed ID: 23261782
Publication DOI: 10.1016/j.carres.2012.11.017
Journal NLM ID: 0043535
Publisher: Elsevier
Correspondence: M.A. Monteiro
Institutions: Department of Chemistry, University of Guelph, Guelph, Ontario, Canada N1G 2W1
Methods: 13C NMR, 1H NMR, NMR-2D, methylation, GC-MS, SDS-PAGE, composition analysis, NMR-1D, immunoblotting, periodate oxidation, conjugation

Bacterial extracellular polysaccharides are known as a cell-bound capsule, a sheath, or a slime, which is excreted into the environment. They play an important role in virulence of medical bacteria and plant-to-symbiont interaction and are used for serotyping of bacteria and production of vaccines. Some exopolysaccharides have commercial applications in industry, and claims of health benefits have been documented for an increasing number of them. Exopolysaccharides have diverse composition and structure, and some contain sugar and non-sugar components that are found in bacterial carbohydrates only. The present article provides an updated collection of the data on exopolysaccharides of various classes of gram-negative and gram-positive bacteria reported until the end of 2019. When known, biosynthesis pathways of exopolysaccharides are treated in a summary manner. References are made to structure and biosynthesis relatedness between exopolysaccharides of different bacterial taxa as well as between bacterial polysaccharides and mammalian glycosaminoglycans.

polysaccharide structure, Gram-negative bacteria, capsule, Biofilm, polysaccharide biosynthesis, gram-positive bacteria, Monosaccharide composition, Bacterial exopolysaccharide, non-sugar component

Publication DOI: 10.1016/B978-0-12-819475-1.00005-5
Publisher: Elsevier
Correspondence: marie-rose.vancalsteren@canada.ca; yknirel@gmail.com
Editors: Barchi J, Kamerling H
Institutions: N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia, Saint-Hyacinthe Research and Development Centre, Agriculture and Agri-Food Canada, Saint-Hyacinthe, QC, Canada

Campylobacter jejuni is the leading cause of human diarrheal diseases and has been designated as one of highly resistant pathogens by the World Health Organization. The C. jejuni capsular polysaccharides feature broad existence of uncommon 6dHepp residues and have proven to be potential antigens to develop innovative antibacterial glycoconjugation vaccines. To address the lack of synthetic methods for rare 6dHepp architectures of importance, we herein describe a novel and efficient approach for the preparation of uncommon d-/l-6dHepp fluorides that have power as glycosylating agents. The synthesis is achieved by a C1-to-C5 switch strategy relying on radical decarboxylative fluorination of uronic acids arising from readily available allyl d-C-glycosides. To further showcase the application of this protocol, a structurally unique hexasaccharide composed of →3)-β-d-6didoHepp-(1→4)-β-d-GlcpNAc-(1→ units, corresponding to the capsular polysaccharide of C. jejuni strain CG8486 has been assembled for the first time. The assembly is characterized by highly efficient construction of the synthetically challenging β-(1,2-cis)-d-ido-heptopyranoside by inversion of the C2 configuration of β-(1,2-trans)-d-gulo-heptopyranoside, which is conveniently obtained by anchimerically assisted stereoselective glycosylation of the orthogonally protected 6dgulHepp fluoride. Ready accessibility of 6dHepp fluorides and the resulting glycans could serve as a rational starting point for the further development of synthetic vaccines fighting Campylobacter infection.

synthesis, capsular polysaccharides, Campylobacter jejuni, d-/l-6dHepp fluorides

NCBI PubMed ID: 34260212
Publication DOI: 10.1021/jacs.1c05048
Journal NLM ID: 7503056
Publisher: American Chemical Society
Correspondence: Ming Li
Institutions: Key Laboratory of Marine Medicine, Chinese Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China, Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology, Qingdao, China
Methods: 13C NMR, 1H NMR, NMR-2D, TLC, chemical synthesis, chemical methods, UV, RP-HPLC, HR-ESI-MS

Each microbe has the ability to produce a wide variety of sugar structures that includes some combination of glycolipids, glycoproteins, exopolysaccharides and oligosaccharides. For example, bacteria may synthesize lipooligosaccharides or lipopolysaccharides, teichoic and lipoteichoic acids, N- and O-linked glycoproteins, capsular polysaccharides, exopolysaccharides, poly-N-acetylglycosamine polymers, peptidoglycans, osmoregulated periplasmic glucans, trehalose or glycogen, just to name a few of the more broadly distributed carbohydrates that have been studied. The composition of many of these glycans are typically dissimilar from those described in eukaryotes, both in the seemingly endless repertoire of sugars that microbes are capable of synthesizing, and in the unique modifications that are attached to the carbohydrate residues. Furthermore, strain-to-strain differences in the carbohydrate building blocks used to create these glycoconjugates are the norm, and many strains possess additional mechanisms for turning on and off transferases that add specific monosaccharides and/or modifications, exponentially contributing to the structural heterogeneity observed by a single isolate, and preventing any structural generalization at the species level. In the past, a greater proportion of research effort was directed toward characterizing human pathogens rather than commensals or environmental isolates, and historically, the focus was on microbes that were simple to grow in large quantities and straightforward to genetically manipulate. These studies have revealed the complexity that exists among individual strains and have formed a foundation to better understand how other microbes, hosts and environments further transform the glycan composition of a single isolate. These studies also motivate researchers to further explore microbial glycan diversity, particularly as more sensitive analytical instruments and methods are developed to examine microbial populations in situ rather than in large scale from an enriched nutrient flask. This review emphasizes many of these points using the common foodborne pathogen Campylobacter jejuni as the model microbe.

carbohydrates, polysaccharides, Campylobacter jejuni, glycoconjugates, phase-variation

NCBI PubMed ID: 36250013
Publication DOI: 10.3389/fmolb.2022.1015771
Journal NLM ID: 101653173
Publisher: Lausanne: Frontiers Media S.A.
Correspondence: C.M. Szymanski
Institutions: Department of Microbiology and Complex Carbohydrate Research Center, University of Georgia, Athens, GA, United States, Department of Microbiology and Complex Carbohydrate Research Center, University of Georgia, Athens, GA, United States Christine