Curbing gastrointestinal infections by defensin fragment modifications without harming commensal microbiota

Research output: Contribution to journalJournal articleResearchpeer-review

  • Louis Koeninger
  • Lisa Osbelt
  • Anne Berscheid
  • Judith Wendler
  • Jürgen Berger
  • Katharina Hipp
  • Till R. Lesker
  • Marina C. Pils
  • Nisar P. Malek
  • Jensen, Benjamin Anderschou Holbech
  • Heike Brötz-Oesterhelt
  • Till Strowig
  • Wehkamp Jan Wehkamp

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.

Original languageEnglish
Article number47
JournalCommunications Biology
Issue number1
Number of pages11
Publication statusPublished - 2021

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