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 m...

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Veröffentlicht in:	FEBS letters 2007-02, Vol.581 (4), p.587-595
Hauptverfasser:	Bailey, Leslie, Gylfe, Åsa, Sundin, Charlotta, Muschiol, Sandra, Elofsson, Mikael, Nordström, Peter, Henriques-Normark, Birgitta, Lugert, Raimond, Waldenström, Anders, Wolf-Watz, Hans, Bergström, Sven
Format:	Artikel
Sprache:	eng
Schlagworte:	4′,6-diamidino-2-phenylindole Animals Anti-Bacterial Agents - chemistry Anti-Bacterial Agents - pharmacology Anti-Bacterial Agents/chemistry/pharmacology Bacterial Proteins - antagonists & inhibitors Bacterial Proteins - genetics Bacterial Proteins - secretion Bacterial Proteins/antagonists & inhibitors/genetics/secretion C. pneumoniae C. trachomatis Cell Proliferation - drug effects Chemical genetics Chlamydia Chlamydia Infections - microbiology Chlamydia pneumoniae Chlamydia trachomatis Chlamydia trachomatis - cytology Chlamydia trachomatis - drug effects Chlamydia trachomatis/cytology/drug effects Chlamydiales Chlamydophila pneumoniae Chlamydophila pneumoniae - cytology Chlamydophila pneumoniae - drug effects Chlamydophila pneumoniae/cytology/drug effects DAPI Dose-Response Relationship, Drug Down-Regulation - drug effects elementary body Epithelial Cells - cytology Epithelial Cells - drug effects Epithelial Cells - microbiology Epithelial Cells/cytology/drug effects/microbiology FCS fetal calf serum Gene Expression Regulation, Bacterial - drug effects Genes, Bacterial HeLa Cells Hsp90 Human 90 kD heat shock protein gene Humans inclusion membrane localized proteins Incs Inhibitors Medicin och hälsovetenskap Mice MOI multiplicity of infection not detectable ompA outer membrane protein A gene p.i PBS phosphate buffered saline post infection reticulate body T3SS TARP Transcription, Genetic - drug effects Type III secretion type three secretion system tyrosine phosphorylated protein wild-type Y. pseudotuberculosis Yersinia Yersinia Infections Yersinia pseudotuberculosis Yersinia pseudotuberculosis - drug effects Yersinia secretion Ysc
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Zusammenfassung:	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.
ISSN:	0014-5793 1873-3468 1873-3468
DOI:	10.1016/j.febslet.2007.01.013