Extensive Genomic Variation within Clonal Complexes of Neisseria meningitidis

Abstract

Meningococcal disease is a widely distributed complex disease affecting all age categories. It can cause severe meningitis and septicemia, especially in unvaccinated infants and young children. The causative agent, Neisseria meningitidis (Nm), can be phenotypically and genetically differentiated into serogroups and sequence types (STs) and has a highly dynamic population structure. To obtain a deeper understanding of the epidemiology of Nm, we sequenced seven Nm genomes. Large-scale genomic analysis was conducted with these 7 Nm genomes, 27 additional Nm genomes from GenBank, and 4 other Neisseria genomes. We observed extensive homologous recombination in all gene functional categories among different Nm genomes. Homologous recombination is so frequent that it has resulted in numerous chimeric open reading frames, including genes in the capsule biosynthesis cluster and loci targeted by commercial vaccines. Our results reveal that, despite widespread use, evolutionary relationships inferred from the standard seven-gene multilocus sequence typing (MLST) method could not predict virulence gene content or strain phenotype. In fact, up to 28% of the virulence-associated genes could differ between strains of identical STs. Consistent with previous studies, we found that allelic recombination is also associated with alterations in antibiotic susceptibility. Overall, these findings emphasize the extensive genomic plasticity of Nm and the limitations of standard molecular methods to quantify this genotypic and phenotypic diversity.

Genetic and antigenic characterization of invasive endemic serogroup B Neisseria meningitidis from Ontario, Canada, in 2001–2010

“…Of interest, 28 (14.5 %) of the MenB case isolates in Ontario expressed the PorA P1.4 epitope detected by mAb as well as predicted by porA genotyping, and were therefore expected to be covered by the PorA component of the 4CMenB vaccine. Furthermore, we, as well as others, have shown the extensive genomic plasticity of N. meningitidis (Holmes et al, 1999;Marri et al, 2010;Hao et al, 2011). How this property may impact on the MenB vaccine antigens under vaccination pressure will probably require long-term surveillance studies.…”

Homologous Recombination Drives Both Sequence Diversity and Gene Content Variation in Neisseria meningitidis

“…This is attributed to the natural competence of Nm cells for transformation and homologous recombination (Chen and Dubnau 2004; Findlay and Redfield 2009). In fact, a high frequency of homologous recombination was consistently observed in a variety of Nm studies (Feil et al 1999; Holmes et al 1999; Vos and Didelot 2009; Hao et al 2011; Joseph et al 2011). Homologous recombination can bring mutations arising in different genomes together and have a strong impact on pathogenic adaptation (Marri et al 2010; Moradigaravand and Engelstadter 2012).…”

Controlling serogroup B invasive meningococcal disease: the Canadian perspective

“…Another essential feature of the genetics of N. meningitidis is the plasticity of its genome allowing extensive genetic recombination and horizontal gene transfer between strains of the same or related species [21]. Use of newer genome sequencing technology has shed light on what accounts for virulence in N. meningitidis and why certain clonal lineages are maintained.…”