Genotypic and phenotypic comparison of Neisseria meningitidis carriage and invasive disease isolates contemporaneously collected in the Netherlands.

Neisseria meningitidis (Nm), a commensal that colonizes the nasopharynx of 4.5%-24% of healthy humans, can cause invasive meningococcal disease (IMD). We hypothesized that distinct genotypic and/or phenotypic signatures might be found in carriage vs. invasive isolates. Carriage isolates were cultured from nasopharyngeal swabs (n = 267) collected from healthy students (aged 13-21 years) during the 2013 and 2014 school years in the Netherlands. Invasive isolates (n = 214) were cultured from all reported disease cases in the Netherlands from 2012 to 2014. Whole core genome sequences were determined for all isolates and comparisons of selected genotypic markers and phylogenomic associations between carriage and disease isolates were analyzed. While 30% of carriage isolates could not be assigned a genogroup, all the invasive isolates were successfully genogrouped. Genogroup B (MenB) predominated, representing 27% of carriage and 75% of IMD isolates. Sequence type (ST) complex diversity was dominated by four STs (ST-41/44, ST-213, ST-32, and ST-269) in both carriage and disease isolates. FHbp subfamily A variants were prevalent (79%) in carriage, whereas subfamily B variants were more frequent (69.6%) in disease. Carriage and IMD-causing Nm strains display similar ST and phylogenomic profiles; however, an increased FHbp subfamily B prevalence and an enhanced level of FHbp surface expression were noted in MenB disease-causing isolates.