Abstract
Bacterial vaginosis (BV) is a dysbiosis of the vaginal flora characterized by a shift from a Lactobacillus-dominant environment to a polymicrobial mixture including Actinobacteria and Gram-negative bacilli. BV is a common vaginal condition in women and is associated with increased risk of sexually transmitted infection and adverse pregnancy outcomes such as preterm birth. Gardnerella vaginalis is one of the most frequently isolated bacterial species in BV. However, there has been much debate in the literature concerning the contribution of G. vaginalis to the etiology of BV, since it is also present in a significant proportion of healthy women. Here we present a new murine vaginal infection model with a clinical isolate of G. vaginalis. Our data demonstrate that this model displays key features used clinically to diagnose BV, including the presence of sialidase activity and exfoliated epithelial cells with adherent bacteria (reminiscent of clue cells). G. vaginalis was capable of ascending uterine infection, which correlated with the degree of vaginal infection and level of vaginal sialidase activity. The host response to G. vaginalis infection was characterized by robust vaginal epithelial cell exfoliation in the absence of histological inflammation. Our analyses of clinical specimens from women with BV revealed a measureable epithelial exfoliation response compared to women with normal flora, a phenotype that, to our knowledge, is measured here for the first time. The results of this study demonstrate that G. vaginalis is sufficient to cause BV phenotypes and suggest that this organism may contribute to BV etiology and associated complications. This is the first time vaginal infection by a BV associated bacterium in an animal has been shown to parallel the human disease with regard to clinical diagnostic features. Future studies with this model should facilitate investigation of important questions regarding BV etiology, pathogenesis and associated complications.
Highlights
One in three women in the U.S have bacterial vaginosis (BV) [1], a microbial imbalance of the vaginal flora characterized by the absence of normally dominant lactobacilli and overgrowth of complex communities dominated by Gram-negative bacteria and Actinobacteria [2,3]
From our initial experiments we found that the majority of b-estradiol-treated C57/Bl6 mice contained vaginal flora producing large, mucoid colonies on Gardnerella semi-selective media that occluded the smaller G. vaginalis colonies
The presence of epithelial clue cells is a well-established clinical feature of Bacterial vaginosis (BV), we found no examples in the literature measuring whether the relative number of epithelial cells in clinical specimens is increased in women with BV compared to those with normal flora
Summary
One in three women in the U.S have bacterial vaginosis (BV) [1], a microbial imbalance of the vaginal flora characterized by the absence of normally dominant lactobacilli and overgrowth of complex communities dominated by Gram-negative bacteria and Actinobacteria [2,3]. BV can be asymptomatic, maybe even part of a spectrum of ‘normal’ from the patient perspective, but often displays characteristic clinical features, including ‘‘thinning’’ of vaginal fluid secretions, increased pH (.4.5), a fishy odor upon potassium hydroxide treatment, and the presence of clue cells (epithelial cells studded with bacteria) in wet mounts. More than a dozen bacterial species have been associated with BV, the potential causal contributions of each to the biochemical, cellular, and clinical features of BV remain elusive. Several investigations have described the pathogenic potential of some G. vaginalis isolates in cell adhesion and entry, cytolytic toxin production, biofilm formation, and other phenotypes that may reflect virulence [26,35,36,37]
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