P1.58 Lactic acid exerts anti-chlamydia trachomatisactivity on the epithelium by reducing host cell proliferation

Introduction Epidemiological studies have demonstrated that the vaginal microbiota can significantly impact the risk of acquiring sexually transmitted infections. The human vagina often contains Lactobacillus spp., which produce lactic acid and create an acidic environment (pH 3.5–4) thought to reduce vaginal STIs. Unlike high d-lactate producers, Lactobacillus spp. that produce low amounts or no d-lactate, while achieving low pH do not reduce Chlamydia trachomatis infectivity. Further, exposure to culture supernatants from d-lactate producing Lactobacillus spp. reduces epithelial cell proliferation. We tested if low proliferation affects infection. Methods A 3D model of A2EN cervical epithelial cells was exposed to lactic acid (D, L or D/L) at concentrations that produce pH 7, 5.5 and 4 or to several Lactobacillus spp. conditioned media (LCM) and infected with C. trachomatis serovar L2. Lysates from these A2EN cells were used to infect HeLa cells, and IFUs counted to determine infectivity. 2D A2EN cells were exposed to lactic acid, proliferation chemical inhibitors or LCM followed by infection with C. trachomatis L2. Proliferation and infectivity were evaluated by microscopy. Results At pH 4, d-lactate and LCMs from high d-lactate producing vaginal Lactobacillus spp. afforded maximal protection compared to l-lactate. Interestingly, high infectivity was observed with HCl at pH 4, indicating that pH alone is not responsible for this protection. Exposure to d-lactate or LCMs reduced cell proliferation. Chemical cell proliferation inhibitors dramatically reduced C. trachomatis infectivity. Conclusion These results suggest a differential role for vaginal Lactobacillus spp. in protecting against C. trachomatis infections and potentially other STIs. This protection is driven by the production of d-lactate, which acts on epithelial cells by inhibiting cell proliferation, which appears to be required for infection.