Genomic resolution of an aggressive, widespread, diverse and expanding meningococcal serogroup B, C and W lineage

Jay Lucidarme,Dorothea M.C Hill,Holly B Bratcher,Steve J Gray,Mignon Du Plessis,Raymond S.W Tsang,Julio A Vazquez,Muhamed-Kheir Taha,Mehmet Ceyhan,Adriana M Efron,Maria C Gorla,Jamie Findlow,Keith A Jolley,Martin C.J Maiden,Ray Borrow

doi:10.1016/j.jinf.2015.07.007

Abstract

SummaryObjectivesNeisseria meningitidis is a leading cause of meningitis and septicaemia. The hyperinvasive ST-11 clonal complex (cc11) caused serogroup C (MenC) outbreaks in the US military in the 1960s and UK universities in the 1990s, a global Hajj-associated serogroup W (MenW) outbreak in 2000–2001, and subsequent MenW epidemics in sub-Saharan Africa. More recently, endemic MenW disease has expanded in South Africa, South America and the UK, and MenC cases have been reported among European and North American men who have sex with men (MSM). Routine typing schemes poorly resolve cc11 so we established the population structure at genomic resolution.MethodsRepresentatives of these episodes and other geo-temporally diverse cc11 meningococci (n = 750) were compared across 1546 core genes and visualised on phylogenetic networks.ResultsMenW isolates were confined to a distal portion of one of two main lineages with MenB and MenC isolates interspersed elsewhere. An expanding South American/UK MenW strain was distinct from the ‘Hajj outbreak’ strain and a closely related endemic South African strain. Recent MenC isolates from MSM in France and the UK were closely related but distinct.ConclusionsHigh resolution ‘genomic’ multilocus sequence typing is necessary to resolve and monitor the spread of diverse cc11 lineages globally.

Highlights

The Gram-negative bacterium Neisseria meningitidis, the meningococcus, is principally a commensal that colonises the nasopharynx of approximately 10% of humans
Meningococcal population structure has been studied with multilocus sequence typing (MLST) which classifies meningococci into clonal complexes
Most invasive isolates belong to a limited number of ccs, which correspond to the hyperinvasive lineages first identified by multilocus enzyme electrophoresis (MLEE).[3]

Summary

Introduction

The Gram-negative bacterium Neisseria meningitidis, the meningococcus, is principally a commensal that colonises the nasopharynx of approximately 10% of humans. It is a leading cause of meningitis and septicaemia, being associated with sporadic cases, outbreaks and epidemics throughout the world.[1] The principal meningococcal virulence factor is the polysaccharide capsule which defines the serogroup. A recently licensed vaccine against serogroup B organisms, targets subcapsular antigens[2] and was developed in response to safety and efficacy concerns surrounding the B polysaccharide. Meningococcal population structure has been studied with multilocus sequence typing (MLST) which classifies meningococci into clonal complexes (ccs).

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Discussion

Conclusion