Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, 208952, United States.
Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, 59840, United States.
Pathog Dis. 2023 Jan 17;81. doi: 10.1093/femspd/ftad026.
Chlamydia trachomatis is an obligate intracellular bacterium that causes blinding trachoma and sexually transmitted disease. The chlamydial plasmid is a critical virulence factor in the pathogenesis of these diseases. Plasmid gene protein 4 (Pgp4) plays a major role in chlamydial virulence by regulating the expression of both chromosomal genes and Pgp3. Despite the importance of Pgp4 in mediating lytic exit from host cells the pathogenic mechanism by which it functions is unknown. CT084 is a highly conserved chromosomal gene with homology to phospholipase D. We showed CT084 expression is regulated by Pgp4 and expressed late in the chlamydial developmental cycle. To investigate the function of CT084 in chlamydial lytic exit from infected cells, we made a CT084 null strain (ct084::bla) by using Targetron. The ct084::bla strain grew normally in vitro compared to wild-type strain; however, the strain did not lyse infected cells and produced significantly less and smaller plaques. Collectively, our finding shows Pgp4-regulated CT084-mediated chlamydia lytic exit from infected host cells.
沙眼衣原体是一种专性细胞内细菌，可导致致盲性沙眼和性传播疾病。衣原体质粒是这些疾病发病机制中的关键毒力因子。质粒基因蛋白 4（Pgp4）通过调节染色体基因和 Pgp3 的表达，在衣原体的毒力中起主要作用。尽管 Pgp4 在介导从宿主细胞裂解中起着重要作用，但它的作用机制尚不清楚。CT084 是一个与磷脂酶 D 具有同源性的高度保守的染色体基因。我们发现 CT084 的表达受 Pgp4 调控，并在衣原体发育周期的晚期表达。为了研究 CT084 在衣原体从感染细胞裂解中的功能，我们使用 Targetron 构建了 CT084 缺失株（ct084::bla）。与野生型菌株相比，ct084::bla 菌株在体外生长正常；然而，该菌株不能裂解感染的细胞，并且产生的噬菌斑数量明显减少且更小。总之，我们的发现表明 Pgp4 调控的 CT084 介导的衣原体从感染宿主细胞裂解。
