Hou Shuping, Dong Xiaohua, Yang Zhangsheng, Li Zhongyu, Liu Quanzhong, Zhong Guangming
Department of Microbiology & Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA Department of Dermatovenereology, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.
Department of Microbiology & Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA Department of Pharmacology, School of Pharmacy, Hebei North University, Zhangjiakou, Hebei, People's Republic of China.
Infect Immun. 2015 Dec;83(12):4701-9. doi: 10.1128/IAI.00746-15. Epub 2015 Sep 28.
Chlamydia trachomatis infection in the lower genital tract can ascend to and cause pathologies in the upper genital tract, potentially leading to severe complications, such as tubal infertility. However, chlamydial organisms depleted of plasmid or deficient in the plasmid-encoded Pgp3 are attenuated in ascending infection and no longer are able to induce the upper genital tract pathologies, indicating a significant role of Pgp3 in chlamydial pathogenesis. We now report that C. trachomatis Pgp3 can neutralize the antichlamydial activity of human cathelicidin LL-37, a host antimicrobial peptide secreted by both genital tract epithelial cells and infiltrating neutrophils. Pgp3 bound to and formed stable complexes with LL-37. We further showed that the middle region of Pgp3 (Pgp3m) was responsible for both the binding to and neutralization of LL-37, suggesting that Pgp3m can be targeted for attenuating chlamydial pathogenicity or developed for blocking LL-37-involved non-genital-tract pathologies, such as rosacea and psoriasis. Thus, the current study has provided significant information for both understanding the mechanisms of chlamydial pathogenesis and developing novel therapeutic agents.
下生殖道的沙眼衣原体感染可上行至并导致上生殖道病变，可能引发严重并发症，如输卵管性不孕。然而，缺乏质粒或质粒编码的Pgp3存在缺陷的衣原体菌株在上行感染中会减弱，且不再能够诱发上生殖道病变，这表明Pgp3在衣原体致病过程中发挥着重要作用。我们现在报告，沙眼衣原体Pgp3可以中和人cathelicidin LL-37的抗衣原体活性，LL-37是一种由生殖道上皮细胞和浸润的中性粒细胞分泌的宿主抗菌肽。Pgp3与LL-37结合并形成稳定复合物。我们进一步表明，Pgp3的中间区域（Pgp3m）负责与LL-37的结合及中和作用，这表明Pgp3m可作为减弱衣原体致病性的靶点，或用于开发阻断涉及LL-37的非生殖道病变（如酒渣鼻和银屑病）的药物。因此，当前的研究为理解衣原体致病机制和开发新型治疗药物提供了重要信息。
