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Title: Characterization of essential glycan transfer and assembly processes in Burkholderia cenocepacia
Author: Mohamed , Yasmine Fathy Mohamed Mahmoud
ISNI:       0000 0004 6058 9320
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2016
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Burkholderia cenocepacia is an opportunistic pathogen causing chronic lung infections in patients with cystic fibrosis, which are difficult to treat, creating a pressing need for alternative prevention and control measures. B. cenocepacia possesses several glycoforms, encompassing the peptidoglycan, lipopolysaccharide and glycoproteins, which are crucial for viability and bacterial cell functioning. The biosynthetic machineries of these glycoconjugates are essential components in determining the final structural composition of bacterial cells, and share a common theme. In this study, three critical components involved in glycan transport and assembly in B. cenocepacia were characterized. First, MurJBc was identified as the peptidoglycan cell wall flippase responsible for the transport of lipid II molecules across the inner membrane to be incorporated into the growing peptidoglycan mesh. MurJ was essential for viability of B. cenocepacia and peptidoglycan synthesis. Second, the protein O-glycosylation cluster, which encodes the necessary proteins for the stepwise assembly of the lipid-linked O-glycan in the cytoplasm and its translocation across the inner membrane prior to the glycan incorporation to target proteins, was unravelled. Results uncovered that all Burkholderia share a common glycan that is antigenic in humans. Furthermore, dramatic pleiotropic phenotypes were associated with protein O-glycosylation in B. cenocepacia, which demonstrates that this process is critical for the normal physiology of these bacteria. Third, LpxLBc was shown to be the only late acyltransferase responsible for penta-acylation of lipid A in B. cenocepacia. It has an important role in LPS transport and survival under stress conditions including the intracellular environment of macrophages. In conclusion, data in this thesis support the notion that the glycan transport and assembly machineries in Burkholderia are required for the ability of this bacterium to thrive in different niches. Further, this work exposes novel antibiotic targets and potential vaccine antigens for future development into therapeutic alternatives to control Burkholderia infections.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available