title: Small molecule inhibitor of type three secretion suppresses acute and chronic Chlamydia trachomatis infection in a novel urogenital Chlamydia model.
abstract: 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.
authors.affiliation: Gamaleya Institute of Epidemiology and Microbiology, Ministry of Health Russian Federation, Gamaleya Street 18, Moscow 123098, Russia.
authors.forename: Ekaterina A
authors.initials: EA
authors.lastname: Koroleva
authors.affiliation: Gamaleya Institute of Epidemiology and Microbiology, Ministry of Health Russian Federation, Gamaleya Street 18, Moscow 123098, Russia.
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Kobets
authors.affiliation: Gamaleya Institute of Epidemiology and Microbiology, Ministry of Health Russian Federation, Gamaleya Street 18, Moscow 123098, Russia.
authors.forename: Egor S
authors.initials: ES
authors.lastname: Zayakin
authors.affiliation: Gamaleya Institute of Epidemiology and Microbiology, Ministry of Health Russian Federation, Gamaleya Street 18, Moscow 123098, Russia.
authors.forename: Sergei I
authors.initials: SI
authors.lastname: Luyksaar
authors.affiliation: Gamaleya Institute of Epidemiology and Microbiology, Ministry of Health Russian Federation, Gamaleya Street 18, Moscow 123098, Russia.
authors.forename: Ludmila A
authors.initials: LA
authors.lastname: Shabalina
authors.affiliation: Gamaleya Institute of Epidemiology and Microbiology, Ministry of Health Russian Federation, Gamaleya Street 18, Moscow 123098, Russia.
authors.forename: Naylia A
authors.initials: NA
authors.lastname: Zigangirova
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002690:Chlamydia Infections / Q000188:drug therapy*; D002692:Chlamydia trachomatis / Q000187:drug effects*; D005260:Female; D051379:Mice; D008811:Mice, Inbred DBA; D054852:Small Molecule Libraries / Q000494:pharmacology*; D014621:Vagina / Q000382:microbiology*
chemical_list: D000900:Anti-Bacterial Agents; D054852:Small Molecule Libraries