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Engineered Cyclotides with Potent Broad in Vitro and in Vivo Antimicrobial Activity.

ABSTRACT: 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.

SUBMITTER: Ganesan R

PROVIDER: S-EPMC8410672 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Engineered Cyclotides with Potent Broad in Vitro and in Vivo Antimicrobial Activity.

Ganesan Rajasekaran R Dughbaj Mansour A MA Ramirez Lisa L Beringer Steven S Aboye Teshome L TL Shekhtman Alexander A Beringer Paul M PM Camarero Julio A JA

Chemistry (Weinheim an der Bergstrasse, Germany) 20210806 49

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 cycloti ...[more]

PMID: 34159664

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