Characterization of Pili Phosphorylcholine Modification in Neisseria meningitidis

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Jennings, Michael P

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Jen, Freda E

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2023-06-08
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Abstract

Phosphorylcholine (ChoP) is a ubiquitous biomolecule found in various organisms including the platelet-activating factor (PAF) in the mammalian hosts and the surface structures of commensal and pathogenic bacteria such as lipooligosaccharide/lipopolysaccharide (LOS/LPS) and pili. The presence of ChoP on these structures could facilitate bacterial-host interactions through the mimicry mechanism. ChoP has been shown to promote bacterial colonisation by binding to the platelet-activating factor receptor and is essential for pathogenesis. Furthermore, the antigenic activity and immunomodulatory properties of ChoP demonstrate that its significance as a small zwitterionic molecule. The human-adapted bacterial pathogen, Neisseria meningitidis, is the causative agent of meningococcal septicaemia and meningitis. Pili-ChoP modification is one of the most important virulence factors of N. meningitidis and is required for early colonisation of human airway epithelium by mediating adhesion to the platelet-activating factor receptor. Unlike bacteria that contain ChoP-linked glycoconjugates, N. meningitidis does not have the previously identified LOS/LPS core (Lic-1) ChoP biosynthetic pathways. Thus, the pathway(s) required for ChoP biosynthesis prior to post-translational modification are unknown. In this thesis, we aimed to characterize the ChoP biosynthetic pathway in N. meningitidis. [...]

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Thesis (PhD Doctorate)

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Doctor of Philosophy (PhD)

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Institute for Glycomics

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The author owns the copyright in this thesis, unless stated otherwise.

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Subject

Neisseria meningitidis

Phosphorylcholine

Post-translational modification

Bacterial virulence

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