PNNL

Abstract

Bacterial vaginosis (BV) is a highly prevalent state of the vaginal microbiota characterized by increased bacterial taxonomic diversity and decreased abundance of lactobacilli. The factors that drive this shift in bacterial community composition are poorly understood. We characterized differences between the vaginal proteomes of people with and without BV using untargeted metaproteomics to identify host and bacterial proteins in 29 cervicovaginal lavage samples. We identified multiple differences, including an increased abundance of the host epithelial repair protein transglutaminase 3 in samples from participants with BV, an observation which we confirmed by enzyme-linked immunosorbent assay in a separate set of cervicovaginal samples. We also performed an analysis of bacterial proteins to tie specific metabolic processes to different species of bacteria. This analysis revealed that both commensal Lactobacillus crispatus and Gardnerella spp. make pullulanase enzymes in vivo that facilitate metabolism of vaginal glycogen. A diverse assortment of BV-associated bacteria produced glutamate dehydrogenases for ammonia secretion and/or assimilation. We also found Dialister micraerophilus and Fannyhessea vaginae expressed separate, complementary enzymes in the biosynthetic pathway for the malodorous polyamine putrescine. We measured polyamine production of mono- and co-cultures of these bacteria and confirmed D. micraerophilus and F. vaginae produce higher concentrations of putrescine when grown together. This result represents a novel synergistic metabolic interaction between BV-associated bacteria. Understanding these interactions may lead to new approaches for disrupting BV communities to promote a healthy vaginal microbiota.