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Title: Regulation of class II pilin gene expression in Neisseria meningitidis
Author: Lobanovska, Mariya
ISNI:       0000 0004 7653 8325
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2018
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Neisseria meningitidis expresses multi-component organelles called Type four pili (Tfp), which are key virulence factors involved in interactions with host cells. Pilin (PilE) is the main component of Tfp and N. meningitidis can express either class I pilins that undergo antigenic variation or class II pilins, which are highly conserved. The region upstream of the pilE gene contains two putative promoters which are recognised by distinct sigma factors: sigma70 family and sigmaN. We aimed to investigate regulation of class II pilE by characterising the role of multiple sigma factors in class II pilE transcription. We confirmed the presence of conserved sigma70 family- and sigmaN-dependent promoter sequences in a large collection of meningococcal genomes. We show that the promoters are functional in E. coli, however in N. meningitidis PilE expression under steady state is initiated from the sigma70 family-dependent promoter. Furthermore, neither the absence nor overexpression of sigmaN had any effect on pilin levels in N. meningitidis which indicates that sigmaN does not contribute to class II pilin regulation, and also suggests that sigmaN does not function as a -12/-24 sequence-dependent activator. Strikingly, Neisseria elongata sigma N, which is known to function as an activator of pilE in commensal N. elongata, was able to reduce meningococcal pilin expression. The negative effect exerted by N. elongata sigmaN on class II pilin expression raises a possibility that in pathogenic Neisseria the sigma-dependent network responsible for the expression of pilE has been modified to maintain Tfp expression, considering their key role in colonisation and pathogenesis. Studying transcription patterns of virulence factors offers an interesting possibility to understand features that define pathogenic Neisseria. We analysed sigmaH regulon in N. meningitidis by RNA sequencing and our results suggest that sigmaH might be implicated in the response to diverse stimuli including the canonical heat shock response. In summary, results presented here provide new insights into class II pilE regulation and the role of sigmaH in N. meningitidis. Future work will focus on identifying signalling networks that govern pilE expression in response to environmental stimuli and will explore the sigma factor cross-talk in pathogenic Neisseria. This will expand our knowledge of meningococcal adaptation to niches within the host.
Supervisor: Exley, Rachel ; Tang, Christoph Sponsor: Anatoliy Denisenko Charitable Fund
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Microbiology