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

Author:

Green Luke R1,Dave Neelam1,Adewoye Adeolu B1,Lucidarme Jay2,Clark Stephen A2,Oldfield Neil J3,Turner David P J3,Borrow Ray2,Bayliss Christopher D1ORCID

Affiliation:

1. Department of Genetics and Genome Biology, University of Leicester, Leicester

2. Meningococcal Reference Unit, Public Health England, Manchester Royal Infirmary, Manchester

3. School of Life Sciences, University of Nottingham, Nottingham, United Kingdom

Abstract

AbstractBackgroundSince 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.MethodsRepeat 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.ResultsSignificant 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.ConclusionsElevated 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.

Funder

Medical Research Council

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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