Curbing gastrointestinal infections by defensin fragment modifications without harming commensal microbiota
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- Curbing gastrointestinal infections by defensin fragment modifications without harming commensal microbiota
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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 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.
Originalsprog | Engelsk |
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Artikelnummer | 47 |
Tidsskrift | Communications Biology |
Vol/bind | 4 |
Udgave nummer | 1 |
Antal sider | 11 |
ISSN | 2399-3642 |
DOI | |
Status | Udgivet - 2021 |
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ID: 256517162