Parallel evolution of group B Streptococcus hypervirulent clonal complex 17 during carriage and disease. GBS CC17 evolution in carriage and disease

Group B Streptococcus (GBS) is a commensal of the gastrointestinal and genitourinary tracts, while a prevailing cause of neonatal disease worldwide. Of the various clonal complexes (CCs), CC17 is over-represented in GBS-infected newborns for reasons that are still largely unknown. Here, we report a comprehensive analysis of 626 CC17 isolates collected worldwide, identifying the genetic traits behind their successful adaptation to humans and the underlying differences between carriage and clinical strains. Comparative analysis with 923 GBS genomes belonging to CC1, CC19 and CC23 revealed that the evolution of CC17 is highly distinct from that of other human-adapted lineages, and recurrently targets functions related to nucleotide and amino acid metabolism, cell adhesion, regulation and immune evasion. We show that the most distinctive features of disease-specific CC17 isolates were frequent mutations in the virulence-associated CovS and Stk1 kinases, underscoring the crucial role of the entire CovRS regulatory pathway in modulating the pathogenicity of GBS. Importantly, parallel and convergent evolution of major components of the bacterial cell envelope, such as the capsule biosynthesis operon, the pilus and Rib, reflects adaptation to host immune pressures and should be taken into account in the ongoing development of a GBS vaccine. The presence of recurrent targets of evolution not previously implicated in virulence also opens the way for uncovering new functions involved in host colonization and in GBS pathogenesis.