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

• 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Keyword

Animals

Anti-Bacterial Agents/chemistry/*pharmacology

Bacterial Proteins/*antagonists & inhibitors/genetics/*secretion

Cell Proliferation/drug effects

Chlamydia Infections/*microbiology

Chlamydia trachomatis/cytology/drug effects

Chlamydophila pneumoniae/cytology/*drug effects

Dose-Response Relationship; Drug

Down-Regulation/drug effects

Epithelial Cells/cytology/drug effects/microbiology

Gene Expression Regulation; Bacterial/drug effects

Genes; Bacterial

Hela Cells

Humans

Mice

Transcription; Genetic/drug effects

Yersinia Infections

Yersinia pseudotuberculosis/*drug effects

Publication and Content Type

ref (subject category)

art (subject category)