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Engineered Cyclotides with Potent Broad in Vitro and in Vivo Antimicrobial Activity
Author(s) -
Ganesan Rajasekaran,
Dughbaj Mansour A.,
Ramirez Lisa,
Beringer Steven,
Aboye Teshome L.,
Shekhtman Alexander,
Beringer Paul M.,
Camarero Julio A.
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202101438
Subject(s) - antimicrobial , in vivo , antibiotics , microbiology and biotechnology , peritonitis , bacteremia , in vitro , antibiotic resistance , biology , medicine , biochemistry
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.