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Sequence variation in the porB gene from B:P1.4 meningococci causing New Zealand's epidemic
Kristin H Dyet1, Diana R Martin
1Communicable Disease Group, Institute of Environmental Science and Research, Porirua, New Zealand.
Abstract:
Since mid-1991, New Zealand has experienced an epidemic of meningococcal disease. The epidemic has been caused by serogroup B meningococci expressing PorA type P1.7-2,4, belonging to the ST-41/ST-44 complex, lineage III. Most B:P1.7-2,4 meningococci express type 4 PorB (87.0%), although case isolates with porB other than type 4 have been identified throughout the duration of the epidemic. To assess the genetic relatedness of case isolates with an alternative porB gene, multilocus restriction typing validated against multilocus sequence typing was used. This determined that B:P1.7-2,4 meningococci with a porB gene that was other than type 4 had the same clonal origin. It was concluded that strains with alternative porB genes had diverged from the original type 4 porB. Variation in porB was also shown to be associated with the uptake of DNA encoding one or two of the PorB variable regions leading to mosaic porB. Point mutation rather than horizontal transfer and recombination was implicated as the mechanism of sequence variation in some strains. This work will serve as a reference point to determine if the administration of a strain-specific vaccine increases the level of porB divergence and variation already observed in New Zealand case isolates. It also complements the study undertaken of PorA stability which showed that variation in P1.7-2,4 PorA was almost exclusively due to deletions in the P1.4 epitope of the epidemic strain.
Insights
Meningococcal disease in New Zealand is linked to specific bacteria strains. Researchers found that variations in the porB gene, while originating from a common source, suggest divergence from the original strain, impacting vaccine development strategies.
Area of Science:
- Microbiology
- Epidemiology
- Genetics
Background:
- New Zealand has faced a meningococcal disease epidemic since 1991.
- The epidemic is primarily caused by serogroup B meningococci (B:P1.7-2,4), belonging to the ST-41/ST-44 complex, lineage III.
- While most epidemic strains express type 4 PorB, isolates with alternative porB genes have been detected.
Purpose of the Study:
- To investigate the genetic relatedness of meningococcal isolates exhibiting alternative porB genes.
- To understand the evolutionary mechanisms driving porB variation in epidemic strains.
- To establish a baseline for assessing the impact of strain-specific vaccines on porB divergence.
Main Methods:
- Multilocus restriction typing (MLRT) was employed.
- MLRT results were validated using multilocus sequence typing (MLST).
- Analysis focused on the genetic origins and variation of the porB gene in case isolates.
Main Results:
- Isolates with alternative porB genes share a common clonal origin with the predominant B:P1.7-2,4 strain.
- Strains with non-type 4 porB genes are considered divergent descendants of the original type 4 porB strains.
- PorB variation is linked to mosaic gene formation, potentially through point mutation rather than horizontal gene transfer.
Conclusions:
- Alternative porB genes in meningococcal isolates represent divergence from the primary epidemic strain.
- Point mutation appears to be a significant mechanism for porB sequence variation.
- This study provides crucial data for monitoring porB evolution in response to potential vaccine interventions.
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