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Characterising two genomic islands involved in metabolism in Neisseria meningitidis

Chu, Adrian Jun (2017) Characterising two genomic islands involved in metabolism in Neisseria meningitidis. PhD thesis, University of York.

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Meningococcal meningitis is endemic in sub-Saharan Africa while sporadic outbreaks burden the developed world by preying on the young and immunocompromised. The causal pathogen Neisseria meningitidis exclusively colonises the human nasopharynx. With a relatively concise genome, it can invade across multiple bodily compartments, which can be highly debilitating and life-threatening. Nine genomic “islands” have been identified in N. meningitidis and N. gonorrhoeae, absent from their commensal cousin N. lactamica. Many are predicted to have roles in bacterial transport, metabolism and regulation. Genomic Island 5 contains three genes and was correctly annotated to encode enzymes involved in the synthesis of the polyamine putrescine, protecting bacteria from oxidative stress. Mutant N. meningitidis lacking these genes grew poorly in rich media. The lesion can be restored by putrescine supplementation or gene complementation. Genomic Island 3 contains two genes poorly annotated to be spermidine-synthesising – a higher polyamine. Mutant N. meningitidis lacking these genes, however, grew poorly in chemically-defined media. Shuffling amino acid profiles and culturing with a labelled arginine isotope suggest a role in the acquisition and metabolism of arginine and glutamine, which are key to meningococcal maintenance. Enhanced systems circumventing host resource-denial, scavenging amino acids and resisting challenges from free radicals are examples of virulence. These islands are believed to support the general fitness of N. meningitidis as a highly competitive commensal but paradoxically “accidental” pathogen, where disease is a likely a result of risk-taking lifestyles in response to complex microenvironment changes. This behaviour is contrasted by N. gonorrhoeae which prefers recurrent infection episodes and long-term establishment. The closely-related but phenotypically diverse members of the Neisseria genus hence serve as research foci of much interest. In a broader sense, investigating why meningococci conserve such pathogen-specific sequences may help inspire new clinical strategies and provide alternative perspectives towards the biology of similar organisms.

Item Type: Thesis (PhD)
Academic Units: The University of York > Biology (York)
Identification Number/EthosID: uk.bl.ethos.739936
Depositing User: Mr Adrian Jun Chu
Date Deposited: 04 May 2018 16:14
Last Modified: 24 Jul 2018 15:24
URI: http://etheses.whiterose.ac.uk/id/eprint/20114

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