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Potentiation of phase variation in multiple outer membrane proteins during spread of the hyperinvasive Neisseria meningitidis serogroup W ST-11 lineage.
journal contributionposted on 2019-06-03, 13:37 authored by LR Green, N Dave, AB Adewoye, J Lucidarme, SA Clark, NJ Oldfield, DPJ Turner, R Borrow, CD Bayliss
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.
This project was supported by the Medical Research Council [MR/M020193/1]. 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 (https://pubmlst.org/neisseria/) hosted by the University of Oxford and developed with funding from the Wellcome Trust and European Union.
CitationJournal of Infectious Diseases, 2019
Author affiliation/Organisation/COLLEGE OF LIFE SCIENCES/Biological Sciences/Genetics and Genome Biology
- AM (Accepted Manuscript)