Nafamostat mesylate inhibits chlamydial intracellular growth in cell culture and reduces chlamydial infection in the mouse genital tract

Urogenital Chiamydia trachomatis (C. trachomatis) infection is one of the most common bacterial sexually transmitted diseases worldwide. Untreated C. trachomatis infections that ascend to the upper genital tract lead to a series of severe complications. To search for novel antichlamydial drugs, we evaluated the effect of nafamostat mesylate (NM), a synthetic serine protease inhibitor, on chlamydial infection. NM inhibited chlamydial intracellular growth and reduced both the inclusion size and number in cell culture. NM may mainly target the intracellular reticulate bodies for inhibition. NM was also effective in enhancing chlamydial clearance from mouse genital tract when NM was applied to mice via intravaginal inoculation. The vaginal NM did not significantly alter inflammatory cytokine responses in the mouse genital tract. Thus, we have demonstrated a novel role of NM in inhibiting the obligate intracellular bacterium Chiamydia.