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Title: Bioinformatics analyses of genetic variation in genomes of Neisseria meningitidis (the meningococcus)
Author: Al-Maeni, Mohammad Abdul Rahmman Mohammad
ISNI:       0000 0004 6494 561X
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2017
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Genetic variation is one of the key concepts underlying persistence of Neisseria meningitidis in its host and counteracting both innate and adaptive immune responses of the host. The mechanism of evolution involves the combined action of de novo mutation, recombination, and localised hypermutation. This study aimed to understand the contributions of these processes to within host evolution during host persistence of N. meningitidis for a period of months. A study of 40 isolates from one carrier and representing six months persistent carriage showed that de novo mutation resulting in single nucleotide polymorphisms (SNPs) was the major factor in structuring of the population. Allelic variants were subject to dynamic temporal fluctuations through persistence of meningococcal isolates over several months. Conversely, recombination was found to a powerful mechanism for generating SNPs and insertion/deletion within 25 paired isolates from 25 carriers and representing between 1 and 6 months host persistence. The processes of de novo mutation and recombination were infrequent but exhibited trends toward surface antigens especially pilin, porins, iron acquisition and capsule genes. Variation in intergenic regions was also examined in these isolates and a high level of variation was observed in conserved functional patterns of Corriea elements. Three carriers were examined for changes in expression of three phase variable genes (opc, hpuAb, and nalP); these were in the OFF state indicating that there may have been selection for low expression. A further investigation of microevolution within a clonal complex found a low rate of recombination within the 25 CC-174 disease and carriage isolates but it was many folds higher than recombination rates of species forming clonal population. Variable genes were distributed into several schemes including bacterial secretion systems, iron acquisition, capsule, surface antigen, bacterial mobility proteins, and antimicrobial resistance, and toxin genes. In conclusion, all the processes of evolution de novo mutation, recombination, and localized hypermutation facilitate asymptomatic carriage of meningococci and microevolution of CC-174.
Supervisor: Bayliss, Christopher ; Schmid, Ralf Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available