Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Small-molecule inhibitors specifically targeting type III secretion.

R Nordfelth1, A M Kauppi, H A Norberg

  • 1Organic Chemistry, Department of Chemistry, Umeå University, SE-90187 Umeå, Sweden.

Infection and Immunity
|April 23, 2005
PubMed
Summary

Novel antibacterial agents targeting the type III secretion (TTS) system were identified. Compound 1 specifically blocks pathogen effector protein delivery, offering a new strategy against bacterial infections.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

The virulence protein Yop5 of Yersinia pseudotuberculosis is regulated at transcriptional level by plasmid-plB1 -encoded trans-acting elements controlled by temperature and calcium.

Molecular microbiology·2017
Same author

Statistical molecular design of balanced compound libraries for QSAR modeling.

Current medicinal chemistry·2010
Same author

Attenuation and preserved immunogenic potential of Yersinia pseudotuberculosis mutant strains evidenced in oral pig model.

Zoonoses and public health·2008
Same author

Virulence blockers as alternatives to antibiotics: type III secretion inhibitors against Gram-negative bacteria.

Journal of internal medicine·2008
Same author

Experimental infections with wild and mutant Yersinia pseudotuberculosis strains in rabbits.

Journal of veterinary medicine. B, Infectious diseases and veterinary public health·2003
Same author

Yersinia species in collagenous colitis: a serologic study.

Scandinavian journal of gastroenterology·2002

Area of Science:

  • Microbiology
  • Molecular Biology
  • Drug Discovery

Background:

  • The type III secretion (TTS) system is crucial for pathogen virulence, enabling effector protein delivery into host cells to suppress immune responses.
  • Homology across different pathogen TTS systems suggests potential for broad-spectrum antibacterial agents targeting this mechanism.
  • Previous research identified small organic molecules with potential to interfere with TTS.

Purpose of the Study:

  • To identify and characterize small molecules that specifically inhibit the type III secretion system.
  • To evaluate the efficacy of identified compounds as potential antibacterial agents.

Main Methods:

  • Utilized reporter gene constructs to screen for compounds targeting the TTS system of *Yersinia pseudotuberculosis*.

Related Experiment Videos

  • Investigated the mechanism of action of a lead compound (compound 1) using in vitro assays and cell-based infection models (HeLa cells).
  • Assessed the effect of compound 1 on Yop effector secretion and translocation.

    • Main Results:

    • Acylated hydrazones of salicylaldehydes were identified as TTS inhibitors.
    • Compound 1 specifically blocked Yop effector secretion in vitro, mimicking calcium's effect.
    • Compound 1 inhibited Yop effector translocation in infected HeLa cells without harming host cells or bacteria.
    • A cell model demonstrated that compound 1 attenuates the pathogen, benefiting the host cell.

    Conclusions:

    • Small compounds targeting the TTS system can be identified and developed.
    • TTS inhibitors represent a promising novel class of antibacterial agents.
    • Compound 1 demonstrates proof of concept for TTS-targeted antibacterial therapy.