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Published on: November 5, 2019
Genomic basis of a polyagglutinating isolate of Neisseria meningitidis
Lavanya Rishishwar1, Lee S Katz, Nitya V Sharma
1School of Biology, Georgia Institute of Technology, Atlanta, Georgia, USA.
Abstract:
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) from a patient with acute meningococcal disease. To this end, we characterized the complete genome sequence of the M16917 isolate and performed a variety of comparative sequence analyses against N. meningitidis reference genome sequences of known serogroups. Multilocus 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, sequence similarity comparisons and phylogenetic analysis showed that the serogroup diagnostic capsule polymerase gene (synD) of M16917 belongs to serogroup B. These results suggest that a capsule-switching event occurred based on homologous recombination at or around the capsule locus of M16917. Detailed analysis of this locus uncovered the locations of recombination breakpoints in the M16917 genome sequence, which led to the introduction of an ∼2-kb serogroup B sequence cassette into the serogroup C genomic background. Since there is no currently available vaccine for serogroup B strains of N. meningitidis, this kind capsule-switching event could have public health relevance as a vaccine escape mutant.
Insights
Genomic analysis revealed a Neisseria meningitidis isolate with a serogroup C background but a serogroup B capsule gene. This capsule-switching event may represent a vaccine escape mutant with public health implications.
Area of Science:
- Microbiology
- Genomics
- Epidemiology
Background:
- Neisseria meningitidis outbreaks are managed using serogroup assays targeting the polysaccharide capsule.
- Conflicting serogroup assay results for invasive meningococcal disease isolates necessitate genomic investigation.
Purpose of the Study:
- To determine the genomic basis for discordant serogroup assay results in a Neisseria meningitidis isolate (M16917).
- To investigate the potential public health implications of capsule-switching events in Neisseria meningitidis.
Main Methods:
- Whole-genome sequencing and comparative genomic analysis of the M16917 isolate.
- Multilocus sequence typing (MLST) and phylogenetic analysis.
- Identification of recombination breakpoints and sequence cassette integration.
Main Results:
- The M16917 isolate belongs to the ST-11 sequence group, typically associated with serogroup C.
- The capsule polymerase gene (synD) of M16917 was identified as belonging to serogroup B.
- Homologous recombination resulted in the insertion of a serogroup B capsule gene cassette into a serogroup C genomic background.
Conclusions:
- A capsule-switching event, involving homologous recombination, occurred in the M16917 Neisseria meningitidis isolate.
- This event resulted in a strain with a serogroup B capsule in a serogroup C background.
- The identified capsule-switching mechanism may lead to vaccine escape mutants, posing a public health concern due to the lack of a serogroup B vaccine.
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