Sequence Variation in the PorB Gene from B:P1.4 Meningococci Causing New Zealand's Epidemic

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.