Experimental evolution and whole genome sequencing as a tool to detect mechanisms of resistance to novel antibiotics

A key strategy for resolving the antibiotic resistance crisis is the development of new drugs with antimicrobial properties. The engineered cationic antimicrobial peptide WLBU2 is a promising compound that can clear Gram-negative and Gram-positive populations and infections even when bacteria are embedded in biofilms. Despite several attempts, no definitive mechanisms of resistance to WLBU2 have been found. Here, we use experimental evolution followed by whole genome sequencing to detect novel genetic pathways and probable mechanisms of resistance to this peptide.