Lateral Gene Transfer Shapes Diversity of Gardnerella spp.

Abstract

Gardnerella spp. are pathognomonic for bacterial vaginosis, which increases the risk of preterm birth and the transmission of sexually transmitted infections. Gardnerella spp. are genetically diverse, comprising what have recently been defined as distinct species with differing functional capacities. Disease associations with Gardnerella spp. are not straightforward: patients with BV are usually infected with multiple species, and Gardnerella spp. are also found in the vaginal microbiome of healthy women. Genome comparisons of Gardnerella spp. show evidence of lateral gene transfer (LGT), but patterns of LGT have not been characterized in detail. Here we sought to define the role of LGT in shaping the genetic structure of Gardnerella spp. We analyzed whole genome sequencing data for 106 Gardnerella strains and used these data for pan genome analysis and to characterize LGT in the core and accessory genomes, over recent and remote timescales. In our diverse sample of Gardnerella strains, we found that both the core and accessory genomes are clearly differentiated in accordance with newly defined species designations. We identified putative competence and pilus assembly genes across most species; we also found them to be differentiated between species. Competence machinery has diverged in parallel with the core genome, with selection against deleterious mutations as a predominant influence on their evolution. By contrast, the virulence factor vaginolysin, which encodes a toxin, appears to be readily exchanged among species. We identified five distinct prophage clusters in Gardnerella genomes, two of which appear to be exchanged between Gardnerella species. Differences among species are apparent in their patterns of LGT, including their exchange with diverse gene pools. Despite frequent LGT and co-localization in the same niche, our results show that Gardnerella spp. are clearly genetically differentiated and yet capable of exchanging specific genetic material. This likely reflects complex interactions within bacterial communities associated with the vaginal microbiome. Our results provide insight into how such interactions evolve and are maintained, allowing these multi-species communities to colonize and invade human tissues and adapt to antibiotics and other stressors.