A classic antibiotic reimagined: Rationally designed bacitracin variants exhibit potent activity against vancomycin-resistant pathogens.

ABSTRACT: Bacitracin is a macrocyclic peptide antibiotic that is widely used as a topical treatment for infections caused by gram-positive bacteria. Mechanistically, bacitracin targets bacteria by specifically binding to the phospholipid undecaprenyl pyrophosphate (C₅₅PP), which plays a key role in the bacterial lipid II cycle. Recent crystallographic studies have shown that when bound to C₅₅PP, bacitracin adopts a highly ordered amphipathic conformation. In doing so, all hydrophobic side chains align on one face of the bacitracin-C₅₅PP complex, presumably interacting with the bacterial cell membrane. These insights led us to undertake structure-activity investigations into the individual contribution of the nonpolar amino acids found in bacitracin. To achieve this w

SUBMITTER: Buijs NP 

PROVIDER: S-EPMC11260088 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature