The proteinaceous biofilm of Gardnerella vaginalis enables a novel enzymatic therapy for bacterial vaginosis

Since it was first reported in the 1950s, bacterial vaginosis (BV) has become a globally vital concern among women of childbearing age. <i>Gardnerella vaginalis</i> is widely recognized as the primary causative agent responsible for BV development. <i>G. vaginalis</i> has a strong tendency to form biofilms which have been linked to widespread antimicrobial tolerance and recurrent or persistent BV episodes. Our study demonstrated that proteins constitute more than 50% of the <i>G. vaginalis</i> biofilm matrix, which significantly protects the bacterium from degradation by lysozyme, and that LasA, an elastase derived from <i>Pseudomonas aeruginosa</i>, effectively disrupts <i>G. vaginalis</i> biofilms and subsequently lyses the bacterial cell wall, leading to cell death. Four candidate biofilm-associated proteins of <i>G. vaginalis</i> were identified using cross-linking mass spectrometry (XL-MS) and subsequently confirmed as LasA substrates through purification and LasA digestion. Peptidoglycan debris was observed after treating the <i>G. vaginalis</i> cell wall extract with LasA. We also found that LasA showed a minimal adverse effect on lactobacilli strains when used <i>in vitro</i>. <i>In vivo</i> studies utilizing murine models artificially infected with <i>G. vaginalis</i> further demonstrated that a single dose of LasA effectively reduces <i>G. vaginalis</i> colonization while exerting a negligible adverse effect on lactobacilli populations. The safety of LasA was further supported by the fact that no negative effects were observed on the treated mice's vaginal tissue sections during the post-treatment administration period.