In Vitro and in Vivo Activity of (Trifluoromethyl)pyridines as Anti- Chlamydia trachomatis Agents

Mohamed A. Seleem, Nicholas A. Wood, Amanda J. Brinkworth, Srikanth Manam, Rey A. Carabeo, Ashlesh K. Murthy, Scot P. Ouellette, Martin Conda-Sheridan

Research output: Contribution to journalArticlepeer-review

Abstract

Chlamydia trachomatis is the leading pathogen in sexually transmitted bacterial infections across the globe. The development of a selective treatment against this pathogen could be an attractive therapeutic option that will reduce the overuse of broad-spectrum antibiotics. Previously, we reported some sulfonylpyridine-based compounds that showed selectivity against C. trachomatis. Here, we describe a set of related compounds that display enhanced anti-chlamydial potency when compared to our early leads. We found that the active molecules are bactericidal and have no impact on Staphylococcus aureus or Escherichia coli strains. Importantly, the molecules were not toxic to mammalian cells. Furthermore, a combination of molecule 20 (the most active molecule) and azithromycin at subinhibitory concentrations acted synergistically to inhibit chlamydial growth. Molecule 20 also eradicated Chlamydia in a 3D infection model and accelerated the recovery of Chlamydia-infected mice. This work presents compounds that could be further developed to be used alone or in combination with existing treatment regimens against chlamydial infections.

Original languageEnglish (US)
Pages (from-to)227-241
Number of pages15
JournalACS infectious diseases
Volume8
Issue number1
DOIs
StatePublished - Jan 14 2022

Keywords

  • 3D culture
  • Chlamydia trachomatis
  • sexually transmitted diseases

ASJC Scopus subject areas

  • Infectious Diseases

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