Chemistry. 2021 Jun 22. doi: 10.1002/chem.202101438. Online ahead of print.
The search for novel antimicrobial agents to combat microbial pathogens is intensifying in response to bioterrorism and rapid drug resistance development to current antibiotic therapeutics. Respiratory failure and septicemia are the leading causes of mortality among hospitalized patients. Here, we report the development of a novel engineered cyclotide with effective broad-spectrum antibacterial activity against several ESKAPE bacterial strains and clinical isolates. The most active antibacterial cyclotide was extremely stable in serum, showed little hemolytic activity and provided protection in vivo in a murine model of P. aeruginosa peritonitis. These results highlight the potential of the cyclotide scaffold for the development of novel antimicrobial therapeutic leads for the treatment of bacteremia.