FHbp variants among meningococci of serogroup B in Italy: Evolution and selective pressure, 2014-2017

Neisseria meningitidis (meningococcus) is the causative agent of invasive meningococcal disease (IMD). Meningococcus of serogroup B (MenB) is one of the main serogroup causing IMD. MenB strains may be prevented by meningococcal B vaccines. In particular, vaccines with Factor H-binding protein (FHbp), classified into two subfamilies (A or B) or in three variants (v1, v2 or v3), are those available. The objective of the study was to investigate the phylogenetic relationships of FHbp subfamilies A and B (variants v1, v2 or v3) genes and proteins, together with their evolution patterns and selective pressure.

Overall, alignments of FHbp nucleotide and protein sequence from 155 MenB samples collected in different parts of Italy, from 2014 to 2017, were analyzed by ClustalW. JModeltest and the Smart Model Selection software were used for the statistical selection of the best-fit substitution models for nucleotide and protein alignments. Site-specific positive and negative selection were estimated through the HYPHY package. The phylogenetic signal was investigated with the likelihood mapping method. The Maximum Likelihood (ML) phylogenetic reconstructions were performed with Phyml.

The phylogenic analysis identified different clusters within the FHbp subfamily A and B variants, confirming sequence diversity. The pattern of selective pressure in our study indicated that subfamily B FHbp sequences are subjected to greater variations and positive selective pressure respect to subfamily A, with 16 positively supported selected sites identified.

The study pointed out the need for continued genomic surveillance for meningococci to monitor selective pressure and amino acidic changes. Monitoring the genetic diversity and molecular evolution of FHbp variants may be useful to investigate genetic diversity which may emerge over time.