Frog-derived synthetic peptides display anti-infective activity against Gram-negative pathogens
Novel antibiotics are urgently needed since bacteria are becoming increasingly resistant to existing antimicrobial drugs. Furthermore, available antibiotics are broad spectrum, often causing off-target effects on host cells and the beneficial microbiome. To overcome these limitations, we used structure-guided design to generate synthetic peptides derived from Andersonin-D1, an antimicrobial peptide (AMP) produced by the odorous frog Odorrana andersonii. We found that both hydrophobicity and net charge were critical for its bioactivity, enabling the design of novel, optimized synthetic peptides. These peptides selectively targeted Gram-negative pathogens in single cultures and complex microbial consortia, showed no off-target effects on human cells or beneficial gut microbes, and did not select for bacterial resistance. Notably, they also exhibited in vivo activity in two preclinical murine models. Overall, we present synthetic peptides that selectively target pathogenic infections and offer promising preclinical antibiotic candidates.
Authors
- César de la Fuente‐Núñez (ORCID: https://orcid.org/0000-0002-2005-5629)
- Esther Broset (ORCID: https://orcid.org/0000-0003-4155-749X)
- Andreia Boaro (ORCID: https://orcid.org/0000-0001-7141-0451)
- Lucía Ageitos (ORCID: https://orcid.org/0000-0002-2422-3773)
- Angela Cesaro (ORCID: https://orcid.org/0000-0003-0435-5346)
- Marcelo D. T. Torres (ORCID: https://orcid.org/0000-0002-6165-9138)
Institutions
- Translational Therapeutics (United States) (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Trends in biotechnology
- Published
- 2025-03-26
- DOI
- https://doi.org/10.1016/j.tibtech.2025.02.007
- Citations
- 5
- Primary Topic
- Antimicrobial Peptides and Activities
- Type
- article
- Field-Weighted Citation Impact
- 5.92
Funders
- Brain and Behavior Research Foundation
- Procter and Gamble
- University of Pennsylvania
- United Therapeutics Corporation
- ACE Foundation
- US-UK Fulbright Commission
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Xunta de Galicia
- National Institutes of Health
- Defense Threat Reduction Agency
- Perelman School of Medicine, University of Pennsylvania
- Penn Skin Biology and Diseases Resource-based Center, University of Pennsylvania
- National Institute of General Medical Sciences
- National Institute of Arthritis and Musculoskeletal and Skin Diseases