De Novo Design of Antibacterial Therapeutics and Immune Modulating Proteins

Abstract

Poor antibiotic stewardship and other factors have accelerated the emergence of bacterial pathogens resistant to many frontline antibiotics, creating an urgent need for new therapeutic strategies. While advances in de novo protein design have enabled the rapid development of protein-based therapeutics against viral pathogens, snake venoms, and cancer targets, few efforts have successfully translated these approaches to bacterial pathogens, in part due to challenges in identifying tractable therapeutic targets. The central question that I sought to address during my PhD was how de novo protein design tools can be applied to identify and exploit bacterial therapeutic vulnerabilities, enabling the development of novel protein-based therapeutics. In this talk, I will outline the design principles and target classes that have emerged as particularly promising for protein-based intervention against infections by multidrug-resistant bacteria.