Population genomics of the Neisseria: evolution of commensalism and virulence. (360G-Wellcome-087622_Z_08_Z)

The evolution of distinct phenotypes within the genus Neisseria, will be studied with a 'population genomics' approach. Isolate collections representative of the genetic and phenotypic diversity of the Neisseria that inhabit human musosa will be employed. Subsets of these collections, chosen on the basis of phenotypic and genetic criteria, will be characterised at the whole genome level with conventional and novel sequencing technologies. The comparison of these data within an evolutionary an d population genetic framework will be enabled by the development of a Bacterial Isolate Genome Sequence Database (BIGSdb). This will enable genome sequence data of any type for an unlimited number of bacterial isolates to be stored, curated, and accessed via a web interface. The BIGSdb platform will enable hierarchical analysis of genome wide data by a variety of criteria and analysis techniques. Four experiments shall be undertaken aimed at identifying genetic changes characteristic of four levels of genetic structure and phenotypic difference in the genus: (i) speciation, by comparison of genomes from different species: (ii) clonal complex within Neisseria meningitidis; (iii) the emergence of the hyperinvasive phenotype in the ST-41/44 complex of the meningococcus; and (iv) the transition of meningococci from carriage to disease.