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Chlamydia  is the most frequently reported sexually transmitted bacteria causing 2.9 million infections annually in the United States. Diagnosis, treatment, and sequelae of chlamydial disease cost billions of dollars each year in the United States alone. Considering that a heparin sulfate-like cell surface receptor is involved in  Chlamydia  infections, we reasoned that sulfated and sulfonated mimics of heparin sulfate would be useful in topical prophylactic prevention of  Chlamydia . In this study, we tested a small, synthetic sulfated agent sulfated pentagalloyl glucoside (SPGG) and three synthetic sulfonated polymers PSS and SPS with average molecular weight in the range of 11 to 1000 kDa for inhibition against  Chlamydia . Infection of HeLa cells with  C. muridarum  or  C. trachomatis  in the presence of increasing concentrations of SPGG or sulfonated polymers were quantified by immunofluorescence of  Chlamydia  inclusions. To determine whether  in vitro  pre-treatment of SPGG inhibits infection of  C. muridarum , HeLa monolayers were incubated with SPGG-containing media, and then infected with  Chlamydia . Our  in vitro  results show that SPGG pre-treatment inhibits  Chlamydia  infection in a dose-dependent manner. In addition, we further determined if SPGG treatment has an inhibitory effect during infection, therefore cell monolayers were infected with  C. muridarum  in the concurrent presence of SPGG. Our results show that SPGG inhibits  C. muridarum  infection with an IC 50  at 10 μg/ml levels. We also tested the inhibitory effect of synthetic polymers PSS and SPS against  Chlamydia  and found inhibition of  C. muridarum  and  C. trachomatis  infections with IC 50  ranging from 0.3 to 0.8 μg/ml. SPGG, PSS, and SPS inhibit formation of  Chlamydia  inclusions in a concentration-dependent manner. For evaluation of  in vivo  efficacy of the most effective agent in blocking  C. muridarum , SPGG, we intravaginally pre-treated mice with SPGG before infection with  C. muridarum . Cervical swabs were collected post-infection to quantify  Chlamydia  inclusions  in vitro . Our  in vivo  data show that the SPGG-treated group has a statistically significant reduction of infection compared to the no-treatment control. Overall, our results show that SPGG could serve as a promising topical inhibitor for preventing  Chlamydia  infection.

A Synthetic, Small, Sulfated Agent Is a Promising Inhibitor of Chlamydia spp. Infection in vivo