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.

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: May 29, 2019
• 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
• Contract Date: May 28, 2019