Pan-GWAS of Streptococcus agalactiae highlights lineage specific genes associated with virulence and niche adaptation

Streptococcus agalactiae (Group B streptococcus, GBS) is a coloniser of the gastrointestinal and urogenital tracts in adults, and an opportunistic pathogen of infants and adults. The worldwide population of GBS is characterised by a series of Clonal Complexes (CCs) with different invasive potentials. CC17 for example is commonly associated with neonatal sepsis and meningitis, while CC1 often causes invasive disease in adults with co-morbidities. The genetic basis of GBS virulence and to what extent different CCs have adapted to different host environments remain uncertain. We have therefore applied a pan-genome wide association study approach to 1988 GBS strains isolated from different hosts and countries, to identify the genes responsible for the phenotypic differences between clonal complexes. Our results show 279 CC-specific genes belonging to metabolic pathways that appear to explain the differential virulence potential of particular CCs, including CC17. Moreover, our analysis leads us to suggest that human-associated GBS CCs have largely evolved in animal hosts before crossing to the human host and then spreading clonally.