Skip to main content

Research Repository

Advanced Search

Potentiation of phase variation in multiple outer membrane proteins during spread of the hyperinvasive Neisseria meningitidis serogroup W ST-11 lineage

Green, Luke R.; Dave, Neelam; Adewoye, Adeolu B.; Lucidarme, Jay; Clark, Stephen A.; Oldfield, Neil J.; Turner, David P.J.; Borrow, Ray; Bayliss, Christopher D.

Potentiation of phase variation in multiple outer membrane proteins during spread of the hyperinvasive Neisseria meningitidis serogroup W ST-11 lineage Thumbnail


Authors

Luke R. Green

Neelam Dave

Adeolu B. Adewoye

Jay Lucidarme

Stephen A. Clark

DAVID TURNER david.turner@nottingham.ac.uk
Clinical Associate Professor

Ray Borrow

Christopher D. Bayliss



Contributors

Abstract

BACKGROUND:
Since 2009, increases in invasive meningococcal disease have occurred in the United Kingdom due to a sub-lineage of the Neisseria meningitidis serogroup W ST-11 clonal complex (the 'original-UK' strain). In 2013, a descendent sub-strain (the '2013-strain') became the dominant disease-causing variant. Multiple outer membrane proteins (OMP) of meningococci are subject to phase-variable switches in expression due to hypermutable simple sequence repeats (SSR). We investigated whether alterations in phase-variable genes may have impacted on the relative prevalence of the original-UK and 2013 sub-strains using multiple disease and carriage isolates.

METHODS:
Repeat numbers were determined by either bioinformatic analysis of whole-genome sequencing data or PCR-amplification and sizing of fragments from genomic DNA extracts. Immunoblotting or sequence-translation identified expression states.

RESULTS:
Significant increases in repeat number were detected between the original-UK and 2013-strains in genes encoding PorA, NadA and two Opa variants. Invasive and carriage isolates exhibited similar repeat numbers but the absence of pilC gene expression was frequently associated with disease.

CONCLUSIONS:
Elevated repeat numbers in OMP genes of the 2013-strain are indicative of higher phase variation rates suggesting that rapid expansion of this strain was due to a heightened ability to evade host immune responses during transmission and asymptomatic carriage.

Citation

Green, L. R., Dave, N., Adewoye, A. B., Lucidarme, J., Clark, S. A., Oldfield, N. J., …Bayliss, C. D. (2019). Potentiation of phase variation in multiple outer membrane proteins during spread of the hyperinvasive Neisseria meningitidis serogroup W ST-11 lineage. Journal of Infectious Diseases, 220(7), 1109–1117. https://doi.org/10.1093/infdis/jiz275

Journal Article Type Article
Acceptance Date May 15, 2019
Online Publication Date May 22, 2019
Publication Date Oct 1, 2019
Deposit Date May 28, 2019
Publicly Available Date Mar 29, 2024
Journal Journal of Infectious Diseases
Print ISSN 0022-1899
Electronic ISSN 1537-6613
Publisher Oxford University Press
Peer Reviewed Peer Reviewed
Volume 220
Issue 7
Pages 1109–1117
DOI https://doi.org/10.1093/infdis/jiz275
Keywords Neisseria meningitidis; serogroup W; Phase variation; Simple sequence repeat; NadA; Opa
Public URL https://nottingham-repository.worktribe.com/output/2096731
Publisher URL https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiz275/5497499