Advisory Committee Chair
Janet Yother
Advisory Committee Members
Kevin Dybvig
Moon H Nahm
David Pritchard
Charles L Turnbough, Jr
Document Type
Dissertation
Date of Award
2017
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
Streptococcus pneumoniae is an important human pathogen. The major virulence factor for S. pneumoniae is the capsular polysaccharide (CPS). Proper expression and localization of the CPS is essential for pathogenesis. Despite the importance of the proper transfer to the cell surface of this virulence factor, no studies have shown the exact structure and attachment to either the cell wall or membrane. Using the S. pneumoniae serotype 2 CPS as a model, which is synthesized by the widespread Wzy mechanism, we found that the CPS attaches to the cell wall β-D-N-acetylglucosamine (GlcNAc) of peptidoglycan (PG) via a direct glycosidic linkage. This type of linkage has also been demonstrated in serotype 8 and serotype 31. While CPS is built on the membrane anchor undecaprenyl-phosphate (Und-P), we demonstrate that the majority of membrane linked CPS is attached via a different lipid, an acylglycerol. Further, we have identified the first reported polysaccharide sulfation in a Gram-positive membrane linked CPS. These results are the first detailed description of a CPS-PG linkage to the cell wall for any organism and to the membrane for any Gram-positive bacteria. Identification of these novel linkages will help ascertain a mechanism for the transfer of CPS and may provide new targets for therapeutic intervention.
Recommended Citation
Larson, Thomas Robbin, "Attachment Of Streptococcus Pneumoniae Capsular Polysaccharide To The Cell" (2017). All ETDs from UAB. 2222.
https://digitalcommons.library.uab.edu/etd-collection/2222