Gardnerella fibrinogen-binding protein as a candidate adherence factor

Bacterial vaginosis (BV), a form of vaginal dysbiosis, is associated with numerous adverse reproductive and obstetric outcomes. <i>Gardnerella</i> spp. are among the key bacteria identified in most BV cases. The formation of a polymicrobial <i>Gardnerella</i>-dominated biofilm on the vaginal epithelium is a characteristic diagnostic marker of BV. <i>Gardnerella</i> colonization and biofilm formation indicate a significant adhesion potential, the determinants of which remain unexplored. In this initial approach to identify <i>Gardnerella</i> adhesins, we analyzed the Cna protein located on the <i>G. vaginalis</i> ATCC 14018 cell surface as determined previously. Structure modeling of Cna (designated Grd Cna) revealed that the protein contains N2 and N3 domains with an immunoglobulin (IgG)-like fold, which shows structural homology to the corresponding domains in SdrD and UafA proteins of the microbial surface component recognizing adhesive matrix molecules (MSCRAMMs) family. A single B domain shares structural similarity with the corresponding domain of Sdr proteins. The R region is rich in PKD repeats, while the C-terminal contains a non-canonical LVNTG cell wall sorting motif. The <i>cna</i> gene was predominantly detected in <i>G. vaginalis</i> isolates but was absent in other commonly identified <i>Gardnerella</i> species isolates. The recombinant Grd Cna protein binds dose-dependently to human fibrinogen but does not interact with fibronectin or collagen types I, III, or IV. Cna-positive <i>G. vaginalis</i> cells adhered to immobilized fibrinogen; however, recombinant Cna did not inhibit this binding, suggesting that Cna may not be a major adhesin mediating <i>G. vaginalis</i> adherence to this ECM component.