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Curbing gastrointestinal infections by defensin fragment modifications without harming commensal microbiota.
Koeninger, Louis Osbelt, Lisa Berscheid, Anne Wendler, Judith Berger, Jügen Hipp, Katharina Marina C Pils, Marina C. Nisar P Malek, Nisar P. Heike Brötz-Oesterhelt, Heike Strowig, Till
Koeninger, Louis
Osbelt, Lisa
Berscheid, Anne
Wendler, Judith
Berger, Jügen
Hipp, Katharina
Marina C Pils, Marina C.
Nisar P Malek, Nisar P.
Heike Brötz-Oesterhelt, Heike
Strowig, Till
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2021-01-08
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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 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.
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Commun Biol. 2021 Jan 8;4(1):47. doi: 10.1038/s42003-020-01582-0.
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Article
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en
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2399-3642
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Attribution 4.0 International