Small Molecule Screening for Inhibitors of the YopH Phosphatase of Yersinia pseudotuberculosis
Bacterial virulence systems are attractive targets for development of new antibacterial agents. Yersinia spp. utilize the type III secretion (T3S) system to secrete and translocate Yersinia outer proteins (Yop effectors) into the cytosol of the target cell and thereby overcome host defenses to successfully establish an infection. Thus, the Yop effectors constitute attractive targets for drug development. In the present study we apply small molecule screening to identify inhibitors of one of the secreted proteins YopH, a tyrosine phosphatase required for virulence. Characterization of seven inhibitors indicated that both competitive and noncompetitive inhibitors were identified with IC50 values of 6–20 μM.
KeywordsEffector Protein Small Organic Molecule Yersinia Enterocolitica Yersinia Pestis Protein Tyrosine Phosphatase Inhibitor
We are grateful for support from the Kempe Foundations, the Carl Trygger’s Foundation, Umea City, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, and the Swedish Governmental Agency for Innovation Systems (VINNOVA).
- Baron C (2009) Antivirulence drugs to target bacterial secretion systems. Curr Opin Microbiol 13:1–6Google Scholar