Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.797540
Title: Investigation into the glycosylation mechanism of polyglycerolphosphate lipoteichoic acid in firmicutes
Author: Percy, Matthew G.
ISNI:       0000 0004 8504 3340
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2015
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Abstract:
Lipoteichoic acid (LTA) constitutes a major component of the cell wall in Gram-positive bacteria belonging to the phylum Firmicutes. The chemical structure of LTA varies between different bacteria. Type I LTA, a polyglycerolphosphate polymer often further decorated with D-alanine and glycosyl moieties, is linked to the outside of the membrane via a glycolipid anchor, and is one of the most common and best characterized structures. While the D-alanyl modification is known to protect bacteria against the action of cationic antimicrobial peptides, the function of the glycosyl modification has never been determined, and the genes involved in this process are unknown. In this work, a bioinformatics approach was used to identify candidate genes encoding glycosyltransferases involved in the LTA glycosylation process in Listeria monocytogenes and Bacillus subtilis. Mutant strains with deletions in these genes were constructed and the absence of glycosyl modifications on LTA confirmed by nuclear magnetic resonance experiments. Using strains lacking glycosyl modification on their LTA, a possible role of this modification in the stress response to NaCl, H2O2, and ethanol was examined. Previous studies on L. monocytogenes suggested that LTA acts as an anchor for cell wall proteins containing GW domains, so named because they possess a glycine - tryptophan dipeptide. In this work, a role of the glycosyl modification on LTA in the retention of the GW domain proteins was explored. However, not only was it found that the glycosyl groups on LTA were dispensable for the binding of GW domain proteins, but also that these proteins were still retained in the cell wall of a L. monocytogenes strain completely lacking LTA. Further experiments using purified GW domain proteins and purified peptidoglycan in binding assays, suggested that GW domain containing proteins are retained in the cell wall by direct binding to the peptidoglycan structure. In summary, this thesis explores possible roles of the glycosyl modification to LTA.
Supervisor: Gründling, Angelika Sponsor: Medical Research Council ; Imperial College London
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.797540  DOI:
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