Medline ® Abstracts for References 14-16

Worldwide, bacterial vaginosis (BV) is the most common vaginal disorder in women of childbearing age. BV is characterized by a dramatic shift in the vaginal microflora, involving a relative decrease in lactobacilli, and a proliferation of anaerobes. In most cases of BV, the predominant bacterial species found is Gardnerella vaginalis. However, pure cultures of G. vaginalis do not always result in BV, and asymptomatic women are sometimes colonized with low numbers of G. vaginalis. Thus, there is controversy about whether G. vaginalis is an opportunistic pathogen and the causative agent of many cases of BV, or whether BV is a polymicrobial condition caused by the collective effects of an altered microbial flora. Recent studies of the biofilm-forming potential and cytotoxic activity of G. vaginalis have renewed interest in the virulence potential of this organism. In an effort to tease apart the aetiology of this disorder, we utilized in vitro assays to compare three virulence properties of G. vaginalis relative to other BV-associated anaerobes. We designed a viable assay to analyse bacterial adherence to vaginal epithelial cells, we compared biofilm-producing capacities, and we assessed cytotoxic activity. Of the BV-associated anaerobes tested, only G. vaginalis demonstrated all three virulence properties combined. This study suggests that G. vaginalis is more virulent than other BV-associated anaerobes, and that many of the bacterial species frequently isolated from BV may be relatively avirulent opportunists that colonize the vagina after G. vaginalis has initiated an infection.

PURPOSE OF REVIEW: Recent evidence supports the view that bacterial vaginosis presents as a polymicrobial biofilm infection. This has far-reaching implications for the pathogenesis, epidemiology, diagnosis and treatment of bacterial vaginosis.

RECENT FINDINGS: Gardnerella vaginalis is presumably the first species to adhere to the vaginal epithelium and then becomes the scaffolding to which other species adhere. Not all G. vaginalis strains do form biofilms: G. vaginalis can be present in the vagina in a planktonic or in a biofilm mode of growth. The presence of planktonic (dispersed) or biofilm-associated (cohesive) G. vaginalis can be reliably shown in urine sediments in both women and men, and there is an absolute concordance in the carriage of biofilm-associated (cohesive) G. vaginalis between women with bacterial vaginosis and their partners. In-vitro data suggest that selected probiotic lactobacilli might be an effective means to conquer the biofilm.

SUMMARY: Future epidemiological research may benefit from biofilm-based urine diagnosis of bacterial vaginosis to a significant extent. The search for noveltherapeutic agents can now be more directed towards the biofilm-breaking agents, but is at present hampered by the lack of a proper in-vitro model of the bacterial vaginosis biofilm.

Bacterial vaginosis is a highly prevalent and poorly understood polymicrobial disorder of the vaginal microbiota, with significant adverse sequelae. Gardnerella vaginalis predominates in bacterial vaginosis. Biofilms of G. vaginalis are present in human infections and are implicated in persistent disease, treatment failure, and transmission. Here we demonstrate that G. vaginalis biofilms contain extracellular DNA, which is essential to their structural integrity. Enzymatic disruption of this DNA specifically inhibits biofilms, acting on both newly forming and established biofilms. DNase liberates bacteria from the biofilm to supernatant fractions and potentiates the activity of metronidazole, an antimicrobial agent used in the treatment of bacterial vaginosis. Using a new murine vaginal colonization model for G. vaginalis, we demonstrate>10-fold inhibition of G. vaginalis colonization by DNase. We conclude that DNase merits investigation as a potential nonantibiotic adjunct to existing bacterial vaginosis therapies in order to decrease the risk of chronic infection, recurrence, and associated morbidities.