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Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids

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Published on: May 4, 2018

Deep learning reveals antimicrobial peptides within prions.

Marcelo D T Torres^1,2,3,4, Fangping Wan^1,2,3,4, Cesar de la Fuente-Nunez^5,6,7,8

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.

Nature Microbiology

|June 19, 2026

Summary

This summary is machine-generated.

Researchers discovered novel antimicrobial peptides, called prionins, derived from prion-related proteins. These prionins show potential in combating bacterial infections and reducing pathogen burden in mice.

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Area of Science:

Biochemistry
Microbiology
Computational Biology

Background:

Prion and prion-like proteins are primarily known for their roles in protein misfolding diseases.
However, amyloidogenic sequences within these proteins may also possess functional roles, including host defense mechanisms.

Purpose of the Study:

To identify novel antimicrobial peptides from prion-related proteins using deep learning.
To characterize the antimicrobial activity and membrane-perturbing properties of these candidate peptides.

Main Methods:

Deep learning screening of 19.3 million protein fragments from 2,897 curated prion-related proteins.
Synthesis and experimental validation of 1,179 candidate antimicrobial peptides (prionins).
Assessment of bacterial inhibition, membrane perturbation, and in vivo efficacy against Acinetobacter baumannii.

Main Results:

Identified 1,179 candidate prionins with antimicrobial potential.
Synthesized 75 prionins, with 59 demonstrating inhibition of bacterial pathogens.
Observed membrane perturbation in 53 synthesized prionins and a reduction in Acinetobacter baumannii infection burden in mice for 2 prionins.

Conclusions:

Prion-related proteins are a source of novel antimicrobial peptides (prionins).
Prionins exhibit significant antibacterial activity and membrane-disrupting capabilities.
These findings suggest a new role for prion proteins in innate immunity and offer potential for developing new antimicrobial therapies.