Antibiotic Drug Discovery

PI: Dr. Toni Kline

Department of Immunology
University of Washington, Seattle, WA

This project combines chemistry and biology to identify new compounds of utility in treating or preventing disease caused by Gram-negative bacteria. The project develops high throughput screens, performs chemical synthesis as part of hit-to-lead chemistry, measures the biological effect of compounds with purified enzymes and in whole bacteria, and studies compound efficacy in small animal models of disease.

Currently three separate programs are active:

  • Gram-negative virulence proteins secretion inhibition by thiazolidinones
  • Diverse strategies including chemical synthesis of analogs and high throughput screen development to discover compounds which inhibit the three steps of the second messenger di-c-GMP metabolism
  • Testing of a quinolone that has no intrinsic antibiotic activity but promotes the activity of the cationic antibiotics polymyxins and aminoglycosides