“I got very excited,” says Torres, a postdoc specializing in chemistry at the University of Pennsylvania.

It took an artificial intelligence algorithm scouring a database of human proteins to help Torres and his team find it.

Peptides are small proteins, or fragments of them.

“I think it speaks to the power of AI,” says ‪César de la Fuente, a bioengineer at the University of Pennsylvania and senior author of the study.

“The fact that they found so many of them,” Van Tyne says of the peptides, “suggests very strongly that it’s not just coincidence—that they exist for a purpose.”.

Along with vaccines and clean water, antibiotics are one of three “pillars” that let humans double our life span since the 1800s, according to de la Fuente.

“All these other interventions in modern medicine would not be possible, or would be a lot harder without effective antibiotics,” says de la Fuente.

But Torres and de la Fuente turned their attention to somewhere even more natural to us: our own bodies.

Antimicrobial peptides with these traits are key weapons for the immune function of all living organisms.

The team had this particular brand of chemical defense in mind when they began their search for antimicrobial peptides.

“We know those patterns—the multiple patterns—that we're looking for,” says de la Fuente.

First, it learned what kills microbes by ingesting a list of peptides that are known to be antimicrobial.

Torres narrowed it down to the 2,603 that come from proteins known to be secreted from cells.

Some were complete small proteins and hormones.

These peptides live along regions called “CUB domains” that exist in proteins involved in a long list of functions like fertilization, making new blood vessels, and suppressing tumors.

Torres also tested how easily bacteria could evolve resistance to the peptides, in comparison to an existing antibiotic called polymyxin B?

“We thought we would have a lot of hits,” he says of the peptides revealed by the AI.

It’s the first time scientists have found antibiotic peptides within proteins unrelated to immune response.

The idea was “really creative,” says Jon Stokes, a biochemist at McMaster University, Canada, who was not involved in the study, but has been prepping his lab to incorporate AI in the search for small molecule antibiotics.

Researchers look for antimicrobials among organisms that live in the soil and the sea, “but this general idea of identifying what I'll call ‘cryptic’ antibiotics that are within us, I think is really cool,” Stokes continues.

AI algorithms can help discover antibiotics in this manner by feeding them known examples of what to look for, then databases of molecules they can search.

“Yeah,” says Stokes, “I’d put my money on that.”

Peptides don’t have a great track record as antibiotics, says Van Tyne

“I don't know that any of these peptides are actually going to become new antibiotics," says Van Tyne

Torres and de la Fuente both appreciate this uphill battle; when they were designing the study, they chose to use peptides that occur naturally in the human body because they are less likely to be toxic

“It opens a door that potentially these could be better antimicrobial peptides than the ones that have been tried to be developed and failed.”

“Our main goal is to have a computer design an antibiotic with very minimal human intervention that will be able to enter clinical trials,” says de la Fuente