VaginalLactobacillusfatty Acid Response Mechanisms Reveal a Novel Strategy for Bacterial Vaginosis Treatment

AbstractBacterial vaginosis (BV), a common syndrome characterized byLactobacillus-deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance byLactobacillus inersinstead ofLactobacillus crispatus, which has more beneficial health associations. Strategies to promoteL. crispatusand inhibitL. inersare thus needed. We show that oleic acid (OA) and similar long-chain fatty acids simultaneously inhibitL. inersand enhanceL. crispatusgrowth. These phenotypes require OA-inducible genes conserved inL. crispatusand related species, including an oleate hydratase (ohyA) and putative fatty acid efflux pump (farE). FarE mediates OA resistance, while OhyA is robustly active in the human vaginal microbiota and sequesters OA in a derivative form that onlyohyA-harboring organisms can exploit. Finally, OA promotesL. crispatusdominance more effectively than antibiotics in anin vitromodel of BV, suggesting a novel approach for treatment.