A Syntenic Pangenome for Gardnerella Reveals Taxonomic Boundaries and Stratification of Metabolic and Virulence Potential across Species

Bacterial vaginosis (BV) is a prevalent condition characterized by an imbalance in the vaginal microbiota, often involving the presence of Gardnerella species. The taxonomic complexity and inconsistent nomenclature of Gardnerella have impeded progress in understanding the role of this genus in health and disease. In this study, we obtained genomes from 392 Gardnerella isolates from asymptomatic individuals and those with BV. With stringent curation of these and additional publicly-available genomes, we conducted a comprehensive genomic analysis (final dataset: n=312). We resolve taxonomic ambiguities using current species thresholds and propose updated Gardnerella nomenclature to facilitate formal naming of these twenty-one identified lineages (eleven species, fifteen subspecies). Syntenic pangenome analysis revealed lineage-specific genetic factors and putative operons associated with virulence, metabolism, and genetic defense mechanisms. We also report on the first cryptic plasmids naturally present within the Gardnerella genus, which should serve to advance mechanistic studies within these species. Our findings provide a unified framework for Gardnerella taxonomy and nomenclature, and advance our understanding of species-specific functional capabilities, with implications for Gardnerella research, diagnostics, and targeted therapeutics in BV.