Exploiting new drug targets in extremely resistant M.abscessus by using small molecule Lipid II binders

摘要

Abstract The public is increasingly at risk to emerging infectious diseases. The prevalence of resistant bacterial pathogens is rendering current antibiotics ineffective, and making it essential that new drugs be developed to fight infections caused by these agents. Lipid II is an essential precursor in bacterial membrane biogenesis and an established, yet underutilized target for antibiotics currently in clinical use. We have for the first time identified small molecule Lipid II binders, based on the interaction between defensins, a family of natural antimicrobial peptides and Lipid II. Characterization of promising Lipid II binders reveals that it uniquely binds to Lipid II and has potent activty against Mycobacteria. This proposal aims to validate and optimize synthetic Lipid II binders as a novel class of antibiotic compounds to combat pathogenic infections caused by these hard-to-treat bacteria.