All ETDs from UAB

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.

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