Identification of Small Molecule Inhibitors of Pseudomonas aeruginosa Exoenzyme S Using a Yeast Phenotypic Screen
2008

Finding Inhibitors for Pseudomonas aeruginosa Exoenzyme S Using Yeast

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Author Information

Author(s): Arnoldo Anthony, Curak Jasna, Kittanakom Saranya, Chevelev Igor, Lee Vincent T., Sahebol-Amri Mehdi, Koscik Becky, Ljuma Lana, Roy Peter J., Bedalov Antonio, Giaever Guri, Nislow Corey, Merrill Rod A., Lory Stephen, Stagljar Igor

Primary Institution: University of Toronto

Hypothesis

Bacterial virulence proteins could act similarly in both yeast and human cells.

Conclusion

The study identified exosin as the first small molecule inhibitor of Exoenzyme S, which protects against Pseudomonas infection.

Supporting Evidence

  • Exosin was shown to directly interact with ExoS in vitro as a competitive inhibitor.
  • Exosin protects CHO cells from lysis during Pseudomonas aeruginosa infection.
  • Yeast homologues of human ExoS targets were identified, validating the yeast model.
  • Six potential inhibitors were identified from a library of over 56,000 compounds.

Takeaway

Researchers used yeast to find a new medicine that can help fight a harmful germ called Pseudomonas aeruginosa.

Methodology

A yeast phenotypic assay combined with a large-scale inhibitor screen was used to identify small molecule inhibitors.

Limitations

The study primarily focused on a single bacterial toxin and its inhibitors.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pgen.1000005

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