Potentiation of Phase Variation in Multiple Outer-Membrane Proteins during Spread of the Hyperinvasive Neisseria meningitidis Serogroup W ST-11 Lineage

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Background: Since 2009, increases in the incidence of invasive meningococcal disease have occurred in the United Kingdom due to a sublineage of the Neisseria meningitidis serogroup W ST-11 clonal complex (hereafter, the "original UK strain"). In 2013, a descendent substrain (hereafter, the "2013 strain") became the dominant disease-causing variant. Multiple outer-membrane proteins of meningococci are subject to phase-variable switches in expression due to hypermutable simple-sequence repeats. We investigated whether alterations in phase-variable genes may have influenced the relative prevalence of the original UK and 2013 substrains, using multiple disease and carriage isolates. Methods: Repeat numbers were determined by either bioinformatics analysis of whole-genome sequencing data or polymerase chain reaction amplification and sizing of fragments from genomic DNA extracts. Immunoblotting and sequence-translation analysis was performed to identify expression states. Results: Significant increases in repeat numbers were detected between the original UK and 2013 strains in genes encoding PorA, NadA, and 2 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 outer-membrane protein 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.

Original languageEnglish
Pages (from-to)1109-1117
Number of pages9
JournalJournal of Infectious Diseases
Volume220
Issue number7
DOIs
Publication statusPublished - 30 Aug 2019

Bibliographical note

Funding Information:
Acknowledgments. The PilC monoclonal antibody was a kind gift of Christopher E. Thomas from the University of North Carolina at Chapel Hill. This publication made use of the Meningitis Research Foundation Genome Library, developed by Public Health England, the Wellcome Trust Sanger Institute, and the University of Oxford, a project funded by Meningitis Research Foundation. This study also made use of the Neisseria Multi Locus Sequence Typing website (available at: https:// pubmlst.org/neisseria/), hosted by the University of Oxford and developed with funding from the Wellcome Trust and European Union [26].

Funding Information:
Financial support. This work was supported by the Medical Research Council (MR/M020193/1).

Publisher Copyright:
© 2019 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America.

Keywords

  • NadA
  • Neisseria meningitidis
  • Opa
  • phase variation
  • serogroup W
  • simple sequence repeat

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