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.
Bailey
Leslie
L
Department of Molecular Biology, Umeå University, SE-90187, Umeå, Sweden.
Gylfe
Asa
A
Sundin
Charlotta
C
Muschiol
Sandra
S
Elofsson
Mikael
M
Nordström
Peter
P
Henriques-Normark
Birgitta
B
Lugert
Raimond
R
Waldenström
Anders
A
Wolf-Watz
Hans
H
Bergström
Sven
S
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002690:Chlamydia Infections / Q000382:microbiology*; D002692:Chlamydia trachomatis / Q000166:cytology / Q000187:drug effects; D016993:Chlamydophila pneumoniae / Q000166:cytology / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D005798:Genes, Bacterial; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D014158:Transcription, Genetic / Q000187:drug effects; D015009:Yersinia Infections; D015011:Yersinia pseudotuberculosis / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins