Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA; Department of Clinic Diagnosis, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA; Department of Obstetrics and Gynecology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Microbes Infect. 2015 Jun;17(6):402-8. doi: 10.1016/j.micinf.2015.02.005. Epub 2015 Mar 6.
Chlamydia trachomatis infection in the lower genital tract, if untreated, can ascend to the upper genital tract, potentially leading to complications such as tubal factor infertility. The ascension involves cell-to-cell spreading, which may require C. trachomatis organisms to overcome mucosal extracellular effectors such as antimicrobial peptides. We found that among the 8 antimicrobial peptides tested, the cathelicidin LL-37 that is produced by both urogenital epithelial cells and the recruited neutrophils possessed a most potent antichlamydial activity. Interestingly, this antichlamydial activity was completely inhibited by CPAF, a C. trachomatis-secreted serine protease. The inhibition was dependent on CPAF's proteolytic activity. CPAF selectively degraded LL-37 and other antimicrobial peptides with an antichlamydial activity. CPAF is known to secrete into and accumulate in the infected host cell cytoplasm at the late stage of chlamydial intracellular growth and may be released to confront the extracellular antimicrobial peptides before the intra-inclusion organisms are exposed to extracellular environments during host cell lysis and chlamydial spreading. Thus, the finding that CPAF selectively targets host antimicrobial peptides that possess antichlamydial activities for proteolysis suggests that CPAF may contribute to C. trachomatis pathogenicity by aiding in ascending infection.
沙眼衣原体感染下生殖道，如果不治疗，可向上生殖道蔓延，可能导致输卵管因素不孕等并发症。这种蔓延涉及细胞间传播，可能需要沙眼衣原体生物克服黏膜细胞外效应物，如抗菌肽。我们发现，在测试的 8 种抗菌肽中，由泌尿生殖道上皮细胞和募集的中性粒细胞产生的 cathelicidin LL-37 具有最强的抗衣原体活性。有趣的是，这种抗衣原体活性完全被沙眼衣原体分泌的丝氨酸蛋白酶 CPAF 抑制。这种抑制依赖于 CPAF 的蛋白水解活性。CPA 选择性地降解 LL-37 和其他具有抗衣原体活性的抗菌肽。CPA 已知在衣原体细胞内生长的晚期分泌到感染宿主细胞的细胞质中，并在包含物内的生物体暴露于细胞外环境之前可能被释放出来，以对抗细胞外的抗菌肽，以应对宿主细胞裂解和衣原体扩散。因此，CPA 选择性地针对具有抗衣原体活性的宿主抗菌肽进行蛋白水解的发现表明，CPA 可能通过帮助上行感染而有助于沙眼衣原体的致病性。
