The plasmid-encoded pGP3 promotes Chlamydia evasion of acidic barriers in both stomach and vagina.

Although Chlamydia trachomatis is a human genital tract pathogen, chlamydial organisms have been frequently detected in both vaginal and rectal swabs of animals and humans. The plasmid-encoded pGP3, a genital tract virulence factor, is essential for C. muridarum to colonize mouse gastrointestinal tract. However, intracolon inoculation to bypass the gastric barrier rescued the colonization of pGP3-deficient C. muridarum mutant, suggesting that pGP3 is required for C. muridarum to reach but not colonize the large intestine. The pGP3-deficient mutant was rapidly cleared in the stomach and was 100-fold more susceptible to gastric killing. Mice genetically deficient in gastrin, a key regulator for gastric acid production, or pharmacologically treated with a proton pump inhibitor rescued the colonization of pGP3-deficient C. muridarum in the gastrointestinal tract. The pGP3-dependent resistance was further recapitulated in vitro with treatments with HCL, pepsin or sarkosyl. In the genital tract, deficiency in pGP3 significantly reduced C. muridarum survival in the mouse vagina and increased C. muridarum susceptibility to vaginal killing by ∼8 times. The pGP3-deficient C. muridarum was more susceptible to lactic acid killing and the pGP3-deficiency also significantly increased C. trachomatis susceptibility to lactic acid. The above observations together suggest that Chlamydia may have acquired the plasmid-encoded pGP3 for overcoming gastric barrier during its adaptation to the gastrointestinal tract and the pGP3-depedent resistance may enable chlamydial evasion of the female lower genital tract barrier during sexual transmission.