Small molecule inhibitors of type III secretion in Yersinia block the Chlamydia pneumoniae infection cycle

FEBS Lett. 2007 Feb 20;581(4):587-95. doi: 10.1016/j.febslet.2007.01.013. Epub 2007 Jan 17.

Abstract

Intracellular parasitism by Chlamydiales is a complex process involving transmission of metabolically inactive particles that differentiate, replicate, and re-differentiate within the host cell. A type three secretion system (T3SS) has been implicated in this process. We have here identified small molecules of a chemical class of acylated hydrazones of salicylaldehydes that specifically blocks the T3SS of Chlamydia. These compounds also affect the developmental cycle showing that the T3SS has a pivotal role in the pathogenesis of Chlamydia. Our results suggest a previously unexplored avenue for development of novel anti-chlamydial drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cell Proliferation / drug effects
  • Chlamydia Infections / microbiology*
  • Chlamydia trachomatis / cytology
  • Chlamydia trachomatis / drug effects
  • Chlamydophila pneumoniae / cytology
  • Chlamydophila pneumoniae / drug effects*
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / microbiology
  • Gene Expression Regulation, Bacterial / drug effects
  • Genes, Bacterial
  • HeLa Cells
  • Humans
  • Mice
  • Transcription, Genetic / drug effects
  • Yersinia Infections
  • Yersinia pseudotuberculosis / drug effects*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins