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Updated: Oct 14, 2025
Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
Published on: December 1, 2020
Mining for encrypted peptide antibiotics in the human proteome.
Marcelo D T Torres1,2,3, Marcelo C R Melo1,2,3, Laurice Flowers4
1Machine Biology Group, Departments of Psychiatry and Microbiology, Institute for Biomedical Informatics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Scientists discovered 2,603 encrypted peptide antibiotics in the human proteome. These novel antimicrobial peptides target bacteria effectively, showing promise for combating drug-resistant infections with minimal resistance development.
Area of Science:
- Microbiology and Infectious Diseases
- Biochemistry and Molecular Biology
- Drug Discovery and Development
Background:
- The rise of antibiotic-resistant bacteria necessitates novel antimicrobial agents.
- Traditional antibiotic discovery methods have yielded limited new classes of drugs.
- The human proteome represents an untapped resource for identifying new antimicrobials.
Purpose of the Study:
- To identify novel encrypted peptide antibiotics from the human proteome using a computational approach.
- To characterize the antimicrobial activity and resistance potential of these identified peptides.
- To evaluate the in vivo efficacy and synergistic potential of these encrypted peptides.
Main Methods:
- Development of an algorithm to mine the human proteome based on physicochemical properties of antimicrobial peptides.
- Identification of 2,603 encrypted peptide candidates from functionally unrelated human proteins.
- In vitro and in vivo (mouse models of skin abscess and thigh infection) testing of peptide efficacy against pathogenic bacteria.
- Assessment of peptide effects on commensal microbiota and bacterial resistance selection.
- Evaluation of synergistic activity among peptides from the same biogeographical origin.
Main Results:
- Discovery of 2,603 encrypted peptide antibiotics encoded within human proteins.
- Demonstrated membrane-targeting bactericidal activity against pathogenic bacteria.
- Modulation of gut and skin commensal microbiota with low propensity for resistance selection.
- Significant anti-infective activity observed in mouse models of skin abscess and thigh infection.
- Synergistic antimicrobial effects shown for peptides from the same biogeographical area.
Conclusions:
- Encrypted peptides within the human proteome represent a rich source of novel antibiotic candidates.
- This algorithmic approach enables rapid mining of proteomic data for antibiotic discovery.
- These findings offer new therapeutic strategies against drug-resistant bacterial infections.
- The synergistic activity of geographically linked peptides suggests potential for combination therapies.
