Genomic Analysis of Serogroup Y Neisseria meningitidis Isolates Reveals Extensive Similarities Between Carriage and Disease-Associated Organisms

BACKGROUND:  Neisseria meningitidis is a frequent colonizer of the human nasopharynx with asymptomatic carriage providing the reservoir for invasive, disease-causing strains. Serogroup Y (MenY) strains are a major cause of meningococcal disease. High resolution genetic analyses of carriage and disease isolates can establish epidemiological relationships and identify potential virulence factors. METHODS:  Whole genome sequence data were obtained from UK MenY carriage isolates from 1997-2010 (n=99). Sequences were compared to those from MenY invasive isolates from 2010 and 2011 (n=73) using a gene-by-gene approach. RESULTS:  Comparisons across 1,605 core genes resolved 91% of isolates into one of eight clusters containing closely related disease and carriage isolates. Six clusters contained carried meningococci isolated in 1997-2001 suggesting temporal stability. One cluster of isolates, predominately sharing the designation Y: P1.5-1,10-1: F4-1: ST-1655 (cc23), was resolved into a sub-cluster with 86% carriage isolates and a second with 90% invasive isolates. These sub-clusters were defined by specific allelic differences in five core genes encoding glycerate kinase (glxK), valine-pyruvate transaminase (avtA), superoxide dismutase (sodB) and two hypothetical proteins. CONCLUSIONS:  High resolution genetic analyses detected long-term temporal stability and temporally-overlapping carriage and disease populations for MenY clones but also evidence of a disease-associated clone.