Dr. Hergenrother joins us in this episode to discuss his groundbreaking work on developing antibiotics for challenging Gram-negative bacterial infections. He delves into the difficulties of creating drugs that can effectively bypass the formidable outer membrane and efflux pumps of Gram-negative pathogens to reach biological targets.

A key point in our conversation revolves around the enzyme FabI - an enzyme that catalyzes the rate-determining step in bacterial fatty acid biosynthesis. While FabI inhibitors have been advanced to clinical trials for Staphylococcus aureus infections, Dr. Hergenrother and his team focus on utilizing them against Gram-negative bacteria.

The discussion leads us to fabimycin, a promising compound resulting from synthesizing a suite of FabI inhibitors in accordance with permeation rules for Gram-negative bac ...