An Integrated Platform for Finding and Developing Novel Antibiotics

Paul J. Hergenrother, along with collaborators at the University of Illinois in the US - Rohit Bhargava, William Metcalf, Gee Lau, and Emad Tajkhorshid - will develop tools that will ultimately lead to novel antibacterial compounds active against K. pneumoniae and other problematic Gram-negative pathogens. While there are many promising antibacterial targets in the periplasm, no convenient method exists to study the exact location of a compound in the Gram-negative cell, and there is no means to direct a compound to a specific subcellular localization. Using a novel imaging technology, the subcellular localization of scores of compounds will be tracked, and through this process the chemical traits that facilitate various subcellular localizations will be elucidated, with a special focus on the periplasm. This information will lead to a streamlined workflow for multi-parameter optimization of antibiotics and will be used to discover novel antibiotic candidates for important biological targets.

This grant is funded by The Wellcome Trust.