Background: Group B Streptococcus (GBS) is a common commensal of the human gastrointestinal and genital tracts but can cause severe disease in neonates, pregnant women, and immunocompromised adults. GBS lineages differ in colonization, virulence, and disease potential. However, the genetic basis of these differences remains underexplored globally.
Methods: We analyzed 24,784 GBS genomes from isolates from human and animal sources, collected across 72 countries, between 1953–2023. Panaroo was used to construct species-level and lineage-specific pangenomes, supported by functional annotations from EggNOG-mapper. Core genes (present in >95% of isolates) were screened using in silico reverse vaccinology to predict vaccine targets based on antigenicity, physicochemical properties, and subcellular localization.
Results: The global GBS pangenome contains 13,300 genes, comprising 1,578 core, 780 intermediate, and 10,942 rare genes. The pangenome size varies significantly between lineages (3,812–7,741 genes), with a median genome size of ~2,000 genes, of which ~1,500 are core. Hypothetical genes with unknown functions dominate the pangenome (7121/13300; 53.50%), followed by DNA replication, transcription, and defence mechanisms genes. Lineage-specific differences were observed across different functional categories. Of 1,578 core genes, 29 were identified as immunogenic, of which 12 were predicted to localize to the cell wall, membrane or extracellular, by PSORTb. This included ABC transporter proteins, metalloproteases, and CHAP and CAMP factor containing proteins.
Conclusion: This study reveals key genetic differences between GBS lineages and identifies potential vaccine targets, providing insights into GBS epidemiology and informing vaccine development.