Will Genome Analysis Elucidate Evolution, Global Transmission and Virulence of Neisseria Meningitidis Lineages?

Neisseria meningitidis is a frequent commensal resident of the oropharyngeal mucosa, carried by at least 10% of the human population in industrialized countries. However, N. meningitidis might penetrate the mucosal membranes and cause life-threatening septicemia and meningitis, commonly with a short time from onset to death. Despite appropriate treatment, the case-fatality rate for invasivemeningococcal disease (IMD) remains around 10% (Goldacre et al., 2003). The bacterium uses different strategies to evade the immune system and survive in different environments, nevertheless, the only truly well-established virulence factor is the polysaccharide capsule. Thirteen serogroups differentiated based on the polysaccharide capsule have been identified, but only six of them (A, B, C, W, X and Y) account for most IMD globally. To control IMD, glycoconjugate vaccines have been developed targeting serogroups A, C,W, and Y (Cohn and Harrison, 2013). It is essential with a universal vaccine also for meningococcal serogroup B (MenB), the predominant etiology of IMD in many countries, which has not been successful due to the poor immunogenicity of the MenB capsule polysaccharide. Therefore, the development of a universal MenB vaccine has focused on conserved protein antigens (Giuliani et al., 2006) and, recent decade, reverse vaccinology (genome-based vaccine discovery) that has resulted in the 4 component meningococcus group B (4CMenB) vaccine (Bexsero; Novartis, MA, US) (O'Ryan et al., 2014). However, due to the selective pressure of 4CMenB newMenB antigenic variants may emerge and reduce the vaccine efficacy. Consequently, careful monitoring of the MenB strain population with high-resolution typing methods is crucial. The genetic diversity and population structure ofN.meningitidis have historically been characterized bymultilocus enzyme electrophoresis (MLEE) and subsequently multilocus sequence typing (MLST) based on seven slowly-evolving housekeeping genes (Maiden et al., 1998). In general, relatively few meningococcal genotypes, clonal complexes or evolutionary lineages have caused most of the IMDworldwide, and these virulentmeningococcal variants diversify as they spread in human populations. As an example, since the 1970s many MenB outbreaks have been caused by strains belonging to the hyperinvasive lineage ST-32 initially described in Norway in 1969 and later described in many other countries worldwide (Caugant et al.,