Small molecule inhibitors of the Yersinia type III secretion system impair the development of Chlamydia after entry into host cells.
BACKGROUND
Chlamydiae are obligate intracellular pathogens that possess a type III secretion system to deliver proteins into the host cell during infection. Small molecule inhibitors of type III secretion in Yersinia, termed INPs (Innate Pharmaceuticals AB) were reported to strongly inhibit Chlamydia growth in epithelial cells. In this study we have analyzed the effect of these drugs on bacterial invasiveness.


RESULTS
We demonstrate that INPs affect Chlamydia growth in a dose dependent manner after bacterial invasion. The efficiency of C. trachomatis L2 and C. caviae GPIC entry into host cells was not altered in the presence of INPs. In C. caviae, entry appears to proceed normally with recruitment of actin and the small GTPases Rac, Cdc42 and Arf6 to the site of bacterial entry.


CONCLUSIONS
INPs have a strong inhibitory effect on Chlamydia growth. However, bacterial invasion is not altered in the presence of these drugs. In the light of these results, we discuss several hypotheses regarding the mode of action of INPs on type III secretion during the Chlamydia infectious cycle.
Muschiol
Sandra
S
Institut Pasteur, Unité de Biologie des Interactions Cellulaires, CNRS URA 2582, Paris, France. sandra.muschiol@smi.se
Normark
Staffan
S
Henriques-Normark
Birgitta
B
Subtil
Agathe
A
D000199:Actins / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002689:Chlamydia / Q000187:drug effects* / Q000254:growth & development*; D002690:Chlamydia Infections / Q000382:microbiology*; D004305:Dose-Response Relationship, Drug; D020558:GTP Phosphohydrolases / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006367:HeLa Cells; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology*; D015007:Yersinia / Q000187:drug effects
D000199:Actins; D000900:Anti-Bacterial Agents; D006834:Hydrazines; C541377:INP 0341; C541376:INP 0400; D020558:GTP Phosphohydrolases