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Bacterial Polysaccharides and Vaccines Thereof

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Title: Bacterial Polysaccharides and Vaccines Thereof
Author: Bertolo, Lisa Suzanne
Department: Department of Chemistry
Program: Chemistry
Advisor: Monteiro, Mario Artur
Abstract: Diarrhea in humans typically results from an imbalance of microbiota in the gastrointestinal tract. Infectious bacteria, both Gram-negative and Gram-positive, remain an important cause of this dysbiosis. Campylobacter jejuni infections have become a major cause of human gastroenteritis over the past 10 years. The capsular polysaccharide of prominent C. jejuni serotypes, the dominant epitope, has been targeted for vaccine development. The research detailed herein characterizes the structure of the capsular polysaccharide (CPS) of two C. jejuni strains belonging to serotype HS:15 by chemical and spectroscopic means. Investigation revealed the CPSs of both strains had similar monosaccharide constituents albeit in different linkages. Clostridium difficile is another bacterium of ill repute, most prominently causing disease after the administration of antibiotics. Infection control is made more difficult by C. difficile spore formation. Characterization of inactivated spores revealed the existence of a glucan with infrequent branching. NMR of intact spores failed to show any anomeric peaks, suggesting that this glucan was located on the inside of the spore. Conserved across C. difficile strains, PS-II from C. difficile K14 was characterized and found to have the same construction as a previously described PS-II. The CPSs of both C. jejuni serotype 15 strains studied and the PS-II isolated from C. difficile K14 were conjugated to carrier proteins (CRM197 and rLTB, respectively). Sera from vaccinated animals were capable of generating respective PS-specific antibodies. Fusobacterium nucleatum has been recently described to have an unknown role in the development of colorectal cancer. The polysaccharide (PS) attributed to the outer surface of this bacterium was structurally elucidated. Interestingly, two non-sugar moieties were also characterized, though their attachment remains to be determined. The structural characterization of PSs offers fundamental knowledge to determine function. Structural diversity, as with C. jejuni, can make this task quite formidable, but pivotal in defining different serotypes and explaining antibody cross-reactivity between serotypes. Conservation of PSs, as with C. difficile, offers an avenue of protection against infection from multiple strains by vaccination. Lastly, characterization of newly important species, as with F. nucleatum, contributes to a growing knowledge base and may offer key insights into disease mechanisms.
URI: http://hdl.handle.net/10214/8788
Date: 2015-03


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