Journal
CHEMISTRY-A EUROPEAN JOURNAL
Volume 27, Issue 49, Pages 12702-12708Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.202101438
Keywords
broad-spectrum antibacterials; cyclotides; multidrug-resistant bacteria; protegrins
Categories
Funding
- National Institutes of Health [R01-GM113636, R35-GM135174, R01-GM085006, P01-HL146367, T90-DE021982]
- SchooI of Pharmacy/Interdisciplinary Research Project
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This study reports 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.
The search for novel antimicrobial agents to combat microbial pathogens is intensifying in response to the rapid development of drug resistance to current antibiotic therapeutics. Respiratory failure and septicemia are the leading causes of mortality among hospitalized patients. Here, the development of a novel engineered cyclotide with effective broad-spectrum antibacterial activity against several ESKAPE bacterial strains and clinical isolates is reported. 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.
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