Adapting antibacterial display to identify serum active macrocyclic peptide antibiotics.

ABSTRACT: The lack of available treatments for many antimicrobial resistant infections highlights the critical need for antibiotic discovery innovation. Peptides are an underappreciated antibiotic scaffold because they often suffer from proteolytic instability and toxicity towards human cells, making in vivo use challenging. To investigate sequence factors related to serum activity, we adapt an antibacterial display technology to screen a library of peptide macrocycles for antibacterial potential directly in human serum. We identify dozens of new macrocyclic peptide antibiotic sequences and find that serum activity within our library is influenced by peptide length, cationic charge, and the number of disulfide bonds present. Interestingly, an optimized version of our most active lead peptide

SUBMITTER: Randall JR 

PROVIDER: S-EPMC10402130 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature