Genomic analyses of polysaccharide capsules in Neisseria species

Thesis

Neisseria meningitidis is one of several Neisseria species that asymptomatically colonise the human nasopharynx. Occasionally, N. meningitidis invades the bloodstream, resulting in invasive meningococcal disease (IMD). In most settings, expression of a serogroup A, B, C, W, X or Y polysaccharide capsule is essential for IMD. Previously, capsules were considered unique to N. meningitidis, among the Neisseria, possibly acquired by horizontal genetic transfer (HGT). In this thesis, genomic analyses further investigate the distribution and evolution of capsules in Neisseria species.

Chapter 2 identifies orthologues of conserved capsule export genes in 13 nonpathogenic Neisseria species. Novel capsule synthesis genes are further characterised and found to resemble those present in other encapsulated bacteria including N. meningitidis, Actinobacillus and Haemophilus. Preliminary 1H NMR results are consistent with some of the structural predictions arising from these comparisons.

Phylogenetic analyses in Chapter 3 indicate that the meningococcal capsule has undergone HGT with other Neisseria species on at least two occasions. Sequence analyses are consistent with hypotheses postulating that the meningococcal capsule was acquired de novo through HGT, with Neisseria subflava identified as a potential donor, but are not sufficient to definitively prove that such an event occurred.

Finally, Chapter 4 explores a more contemporary example of HGT within the meningococcal capsule locus. Capsule switching from serogroup E to serogroup B is shown to be responsible for cases of IMD in clonal complexes cc60 and cc1157. This example is further explored to discuss the interaction between the capsule and the wider genetic profile of meningococci, and their association with IMD.

These analyses expand on previous understanding of the distribution and evolution of the polysaccharide capsule in the Neisseria, and the implications for the epidemiology of IMD. Discussions of this important virulence-associated factor address its enigmatic existence in organisms that principally colonise the nasopharynx without causing disease.

Authors: Clemence, M

• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: bacteria; virulence; evolution; commensals; genomes
• Subjects: Microbiology; Genetics