Prions, the misfolded proteins behind rare and fatal brain diseases, may be hiding something useful: short peptide fragments that kill bacteria. Researchers at the Perelman School of Medicine at the University of Pennsylvania report in Nature Microbiology that they identified 1,179 candidate antimicrobial peptides tucked inside prion and prion-like proteins, and named the new class "prionins."
The team used a deep-learning platform called APEX 1.1, which predicts whether a given amino acid sequence has antibiotic activity, to sift through 19.3 million short fragments drawn from 2,897 prion and prion-like proteins. Screening on that scale by conventional laboratory methods would be impractical, which is part of why nobody had systematically looked in these proteins before.
The idea did not come out of nowhere. Earlier work had shown that fragments of amyloid-beta, the protein central to Alzheimer's disease, and of the cellular prion protein could act against microbes. What the Penn study adds is scale and a broader question: whether proteins most closely associated with neurodegeneration also carry molecular features tied to innate immune defense. If so, the line between "disease protein" and "defense protein" may be less clean than assumed.
For now these are computational predictions of a new place to hunt for drugs, arriving as drug-resistant infections shrink the pool of usable antibiotics. What the findings mean for understanding Alzheimer's or prion disease itself remains an open question rather than an answer.