A new pipeline of first in class antibiotics templated on the bacteriocins

Bacteriocins are proteinaceous toxins produced by bacteria in order to kill other, closely-related strains. Bacteriocins from bacteria which normally colonize the human body hold considerable promise to replace/augment conventional antibiotics; however, despite their potency, these compounds have not evolved to function as therapeutics. As a result, the drug development community urgently needs a generic method able to convert these promising molecules into clinically applicable agents. In this project we will take a model bacteriocin and through iterative structure-function analysis significantly enhance its performance in terms of specificity, stability and potency. This will be achieved through the development of an empirical structure-activity relationship algorithm to generate a range of derivatives exhibiting drug-like properties without compromising the potent bactericidal activity of the original compound. We will then scale-up the manufacture of selected derivatives, demonstrating our capabilities not just in discovery but also in supply. No such combined capability currently exists and this innovation will allow the project partners to gain a unique and pre-eminent position in the market for bacteriocin-derived antibiotics. Keywords: antimicrobial resistance; drug development; bacteriocins.