Neisseria meningitidis M16917 Genome sequencing

Containment strategies for outbreaks of invasive Neisseria meningitidis disease are informed by serogroup assays that characterize the polysaccharide capsule. We sought to uncover the genomic basis of conflicting serogroup assay results for an isolate (M16917) taken from a patient with acute meningococcal disease. To this end, we characterized the complete genome sequence of M16917 and performed a variety of comparative sequence analyses against isolates from known serogroups. Multi-locus sequence typing and whole genome sequence comparison revealed that M16917 is a member of the ST-11 sequence group, which is most often associated with serogroup C. However, phylogenetic analysis showed that the serogroup diagnostic capsule polymerase gene (synD) from M16917 belongs to serogroup B. These results suggested that a capsule switching event occurred based on homologous recombination at or around the capsule locus of M16917. Detailed analysis of this locus uncovered four recombination breakpoints in the M16917 genome sequence, including a breakpoint within synD resulting in a chimeric capsule polymerase. Thus, two separate segments of serogroup B capsule locus genomic sequence were introduced into the serogroup C genomic background via recombination, yielding a hybrid capsular structure. These results suggest that the recombination events underlying capsule switching are more dynamic than previously imagined.