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Curbing gastrointestinal infections by defensin fragment modifications without harming commensal microbiota.


ABSTRACT: The occurrence and spread of multidrug-resistant pathogens, especially bacteria from the ESKAPE panel, increases the risk to succumb to untreatable infections. We developed a novel antimicrobial peptide, Pam-3, with antibacterial and antibiofilm properties to counter this threat. The peptide is based on an eight-amino acid carboxyl-terminal fragment of human ?-defensin 1. Pam-3 exhibited prominent antimicrobial activity against multidrug-resistant ESKAPE pathogens and additionally eradicated already established biofilms in vitro, primarily by disrupting membrane integrity of its target cell. Importantly, prolonged exposure did not result in drug-resistance to Pam-3. In mouse models, Pam-3 selectively reduced acute intestinal Salmonella and established Citrobacter infections, without compromising the core microbiota, hence displaying an added benefit to traditional broad-spectrum antibiotics. In conclusion, our data support the development of defensin-derived antimicrobial agents as a novel approach to fight multidrug-resistant bacteria, where Pam-3 appears as a particularly promising microbiota-preserving candidate.

SUBMITTER: Koeninger L 

PROVIDER: S-EPMC7794397 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Curbing gastrointestinal infections by defensin fragment modifications without harming commensal microbiota.

Koeninger Louis L   Osbelt Lisa L   Berscheid Anne A   Wendler Judith J   Berger Jürgen J   Hipp Katharina K   Lesker Till R TR   Pils Marina C MC   Malek Nisar P NP   Jensen Benjamin A H BAH   Brötz-Oesterhelt Heike H   Strowig Till T   Jan Wehkamp  

Communications biology 20210108 1


The occurrence and spread of multidrug-resistant pathogens, especially bacteria from the ESKAPE panel, increases the risk to succumb to untreatable infections. We developed a novel antimicrobial peptide, Pam-3, with antibacterial and antibiofilm properties to counter this threat. The peptide is based on an eight-amino acid carboxyl-terminal fragment of human β-defensin 1. Pam-3 exhibited prominent antimicrobial activity against multidrug-resistant ESKAPE pathogens and additionally eradicated alr  ...[more]

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