Small molecule inhibitor of type three secretion suppresses acute and chronic Chlamydia trachomatis infection in a novel urogenital Chlamydia model

Biomed Res Int. 2015:2015:484853. doi: 10.1155/2015/484853. Epub 2015 Jan 28.

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.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Chlamydia Infections / drug therapy*
  • Chlamydia trachomatis / drug effects*
  • Female
  • Mice
  • Mice, Inbred DBA
  • Small Molecule Libraries / pharmacology*
  • Vagina / microbiology*

Substances

  • Anti-Bacterial Agents
  • Small Molecule Libraries