Gardnerella vaginalis has been associated with bacterial vaginosis (BV) and preterm birth (PTB) risk, but with little success in being able to identify, treat, and prevent risk. Increasingly, G. vaginalis variants have been differentially associated with these outcomes and associated pathogenic behaviors. These differences have been linked to vast phylogenetic and phenotypic diversity across the named species, G. vaginalis, which has been suggested to represent as many as 13 genomic species. In order to eventually understand, prevent, and treat pathogenic outcomes, we must define a consistent and reliable method to identify G. vaginalis variants. We have demonstrated the ability to identify the presence and abundance of six subspecies G. vaginalis clades in shotgun metagenomic sequencing data, which is an important step in understanding how these clades may shape their microbial communities. Preliminary evidence suggests potential differences in community signatures associated with each clade. We hypothesize six subspecies G. vaginalis clades differ in overall relative transcription rates, transcription of genes related to pathogenicity, and that fold increases of G. vaginalis transcripts in preterm birth vary among the clades. We also hypothesize that G. vaginalis clades differ in phenotypes that relate to the ability to shape the microbial community and host health. We will use paired metagenomic and metatranscriptomic sequencing data to describe G. vaginalis clade transcription in pregnancy and preterm birth. We will also use in vitro assays to assess epithelial adhesion, biofilm formation, and competitive growth against Lactobacillus spp. of the clades. Successful completion of these aims will demonstrate clinically relevant variation among six G. vaginalis clades. Therefore, these aims represent a unique multidisciplinary approach to the systematic understanding of G. vaginalis diversity, which is necessary for identifying health risks in conditions such as BV and PTB, and targeting successful intervention strategies.
These aims will also provide training in both computational and technical skills to foster an independent researcher capable of bridging disciplines to solve complex problems in biomedicine.
In this proposal, we aim to use a multidisciplinary approach to study the impact of Gardnerella vaginalis on the vaginal microbiome and gynecologic and obstetric outcomes. We propose to use multi-omic sequencing data from vaginal swabs collected longitudinally through pregnancies delivered at term or preterm in addition to in vitro comparisons of pathogenic phenotypes of G. vaginalis. Results from this research will have direct applications for improving the association and prediction of health conditions with the vaginal microbiome.
