Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 220, Issue 7, Pages 1109-1117Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiz275
Keywords
Neisseria meningitidis; serogroup W; phase variation; simple sequence repeat; NadA; Opa
Categories
Funding
- Medical Research Council [MR/M020193/1]
- MRC [MR/M020193/1] Funding Source: UKRI
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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 phasevariation rates, suggesting that rapid expansion of this strain was due to a heightened ability to evade host immune responses during transmission and asymptomatic carriage.
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