Koroleva Ekaterina A, Kobets Natalia V, Zayakin Egor S, Luyksaar Sergei I, Shabalina Ludmila A, Zigangirova Naylia A
Gamaleya Institute of Epidemiology and Microbiology, Ministry of Health Russian Federation, Gamaleya Street 18, Moscow 123098, Russia.
Biomed Res Int. 2015;2015:484853. doi: 10.1155/2015/484853. Epub 2015 Jan 28.
Previously, we reported that a compound from a group of thiohydrazides of oxamic acids, CL-55, possessed antichlamydial activity in vitro that was accompanied by a decreased translocation of the type three secretion effector, IncA, into the host cell. In this study, the antichlamydial activity of CL-55 was tested in vivo in DBA/2 mice infected with C. trachomatis serovar D. We found that intravaginal inoculation of DBA/2 mice with the clinically relevant strain, C. trachomatis serovar D, results in a course of infection and pathology similar to that observed in humans. The early stage of infection in this model was characterized by a shedding of Chlamydia in vaginal secretions followed by an ascending infection and inflammation in the upper genital tract. We found that CL-55 possessed antibacterial activity in vivo and was able to control C. trachomatis vaginal shedding, ascending infection, and inflammation in the upper genital organs in DBA/2 mice. Our data provide a proof of concept for the protective effect of the thiadiazinon, CL-55, against chlamydial infection in vivo and support the feasibility of further studies of its potential therapeutic applications.
此前，我们报道过一种源自草氨酸硫酰肼类化合物CL-55在体外具有抗衣原体活性，同时伴有Ⅲ型分泌效应蛋白IncA向宿主细胞内转运减少。在本研究中，我们对CL-55在感染沙眼衣原体D血清型的DBA/2小鼠体内的抗衣原体活性进行了测试。我们发现，用临床相关菌株沙眼衣原体D血清型对DBA/2小鼠进行阴道接种，会导致其感染过程和病理变化与人类相似。该模型感染早期的特征是阴道分泌物中有衣原体脱落，随后是上生殖道的上行感染和炎症。我们发现CL-55在体内具有抗菌活性，能够控制DBA/2小鼠体内沙眼衣原体的阴道脱落、上行感染以及上生殖器官的炎症。我们的数据为噻二嗪酮CL-55在体内对衣原体感染的保护作用提供了概念验证，并支持对其潜在治疗应用进行进一步研究的可行性。
