Neisseria meningitidis is a leading bacterial cause of sepsis and meningitis globally. Beginning with an epidemic among Hajj pilgrims in 2000, capsular group W (W) sequence type (ST) 11 emerged as a leading cause of epidemic meningitis in the African ‘meningitis belt’ and endemic cases in South America, Europe, Middle East and China. Previous genotyping studies were unable to reliably discriminate less virulent W ST-11 strains in circulation since 1970 from the Hajj epidemic strain (Hajj clone). It is also unclear what proportion of more recent W ST-11 disease clusters were caused by direct descendants of the Hajj clone. This work analyzes whole genome sequences of a global collection of over 250 meningococcal strains isolated from patients with invasive meningococcal disease globally from 1970 to 2014 using phylogenetic analyses, detailed examination of the capsule gene cluster (cps) and genes encoding major surface antigens.
We found that all W ST-11 strains were descendants of an ancestral strain that had undergone unique capsular switching events. We identified two distinct, conserved, recombination events within W ST-11 cps genes with W ST-22 and Y ST-23 as most likely donor lineages. In addition, the Hajj clone and its descendants were distinct from other W ST-11 strains in that they shared a common antigen gene profile and had undergone further recombination involving virulence genes encoding factor H binding protein (fHbp), nitric oxide reductase (nor), and nitrite reductase (aniA). These data suggest that the W ST-11 capsular switch involved two separate recombination events and that current global W ST-11 meningococcal disease is caused by strains bearing this capsular switch. Emergence of the Hajj clone may be related to recent acquisition of a distinct antigen-encoding gene profile and variations in meningococcal virulence genes.
This study resolves questions about the Hajj epidemic strain that were unanswered for 15 years. Furthermore, the findings of this study help illuminate genomic factors associated with emergence and evolution virulent meningococcal strains.
Public Health significance: This dissertation provides genomic markers that reliably distinguish epidemic from sporadic W ST-11 strains that are applicable to molecular surveillance of N. meningitidis. Data presented in this work also demonstrate the need for a group W vaccine disease in the meningitis belt that can be potentially used beyond the meningitis belt in South Africa, parts of Latin America, and Europe that are facing the emergence of W ST-11
