Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Department of Microbiology, Immunology & Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Infect Immun. 2019 Apr 23;87(5). doi: 10.1128/IAI.00844-18. Print 2019 Mar.
Although is a human genital tract pathogen, chlamydial organisms have frequently been detected in both vaginal and rectal swab samples of animals and humans. The plasmid-encoded pGP3, a genital tract virulence factor, is essential for to colonize the mouse gastrointestinal tract. However, intracolon inoculation to bypass the gastric barrier rescued the colonization ability of a pGP3-deficient mutant, suggesting that pGP3 is required for to reach but not to colonize the large intestine. The pGP3-deficient mutant was rapidly cleared in the stomach and was 100-fold more susceptible to gastric killing. In mice genetically deficient in gastrin, a key regulator for gastric acid production, or pharmacologically treated with a proton pump inhibitor, the ability of pGP3-deficient to colonize the gastrointestinal tract was rescued. The pGP3-dependent resistance was further recapitulated with treatments with HCl, pepsin, or sarkosyl. In the genital tract, deficiency in pGP3 significantly reduced survival in the mouse vagina and increased susceptibility to vaginal killing by ∼8 times. The pGP3-deficient was more susceptible to lactic acid killing, and the pGP3 deficiency also significantly increased susceptibility to lactic acid. The above-described observations together suggest that may have acquired the plasmid-encoded pGP3 to overcome the gastric barrier during its adaptation to the gastrointestinal tract and the pGP3-dependent resistance may enable chlamydial evasion of the female lower genital tract barrier during sexual transmission.
虽然 是一种人类生殖道病原体，但衣原体生物经常在动物和人类的阴道和直肠拭子样本中被检测到。质粒编码的 pGP3 是一种生殖道毒力因子，对于 在小鼠胃肠道中定植是必不可少的。然而，通过定植于肠道来绕过胃屏障的方法挽救了 pGP3 缺陷的 突变体的定植能力，这表明 pGP3 对于 到达但不是定植大肠是必需的。pGP3 缺陷的突变体在胃中迅速清除，对胃酸杀灭的敏感性增加了 100 倍。在胃泌素缺乏的遗传缺陷小鼠（胃酸产生的关键调节剂）或用质子泵抑制剂进行药理学处理的小鼠中，pGP3 缺陷的 定植胃肠道的能力得到了挽救。pGP3 依赖性抗性还通过 HCl、胃蛋白酶或 sarkosyl 的处理得到了进一步重现。在生殖道中，pGP3 的缺乏显著降低了 在小鼠阴道中的存活能力，并使 对阴道杀伤的敏感性增加了约 8 倍。pGP3 缺陷的 对乳酸的杀灭更敏感，pGP3 的缺乏也显著增加了 对乳酸的敏感性。上述观察结果表明， 可能在适应胃肠道的过程中获得了质粒编码的 pGP3 来克服胃屏障，而 pGP3 依赖性抗性可能使衣原体在性传播过程中逃避女性下生殖道屏障。
