Dissertation

Next generation bacitracin: reimagining a classic antibiotic

Given the accelerating appearance of antimicrobial resistance, there is an urgent need for more fundamental research into novel antibiotic strategies. The work in this thesis helps to address this global problem by developing new antibiotic compounds, inspired by the antibacterial mechanisms of the natural antibiotic bacitracin.

Author: N.P. Buijs
Date: 20 December 2023
Links: Thesis in Leiden Repository

By unravelling the unique mechanism of action that bacitracin employs, we discovered that the inclusion of a small hydrophobic group in key locations of the molecule results in a dramatic enhancement of antibacterial activity, in some cases more than 100 times more potent than bacitracin. Crucially we found that the most potent analogues are particularly active against antibiotic-resistant bacteria including those bearing clinically challenging resistance genes. In doing so we have developed potent next-generation variants of this classic antibiotic and have taken important steps in the fight against antimicrobial resistance.