Plate Nº 25 · recorded October 10, 2026
Biology & EvolutionReported finding
160-Million-Year-Old Peptides Outperform Modern Human Versions
University of Oregon biologists resurrected 160-million-year-old antimicrobial proteins. In lab tests, several outperformed modern human peptides against drug-resistant bacteria.
By Marcus Bennett3 min read665 words
In brief
- Study published August 25, 2026 in PLOS Biology by a University of Oregon team
- Resurrected proteins date back approximately 160 million years to early placental mammals
- Some reconstructed peptides outperformed the corresponding modern human peptide against drug-resistant bacteria in lab tests
- A single amino acid change explained most of the added potency
- Study funded by the National Institutes of Health
A University of Oregon team has resurrected antimicrobial proteins that last circulated in mammals 160 million years ago, and in lab tests some of these ancient peptides beat modern human versions at killing drug-resistant bacteria.
The work, published August 25, 2026, in PLOS Biology, gives evolutionary biologists a fresh set of starting points for designing new infection fighters as standard antibiotics lose effectiveness.
How Did the Research Work?
Graduate student Titas Sil, the paper's lead author, started by comparing lactoferrin gene sequences from living species, including humans and cows. Lactoferrin, an immune protein that circulates in breast milk, tears, saliva, mucus, and most other body fluids, locks away iron that bacteria need to grow.
Sil and her colleagues then used statistical methods called ancestral sequence reconstruction to predict the most likely genetic sequences carried by extinct mammalian ancestors. Joseph Thornton, a former University of Oregon scientist, first developed the technique. Barber's group now occupies Thornton's old lab space.
Sil synthesized the predicted genes, used cells to manufacture the reconstructed proteins, and tested them against four pathogens linked to human disease: Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, and Streptococcus.
What Did They Find?
The oldest resurrected peptides, dating to roughly 160 million years ago, disrupted bacterial membranes but did not kill the microbes. The bacteria appeared to repair the damage and survive.
Versions reconstructed from more recent ancestors, only a few million years back, performed better. In several cases, these younger ancestral peptides beat the corresponding human lactoferrin peptide in lab tests.
A single amino acid change in the peptide chain explained much of the added potency, the team reported. "What was surprising and unexpected was how small changes in these domains could have such large effects," said Matt Barber, senior author and an evolutionary biologist at the UO College of Arts and Sciences.
Why Does This Matter for Antibiotic Resistance?
Antibiotic-resistant infections have become a major global health problem. Barber framed the urgency directly: "For anybody who studies pathogenic bacteria, it's always in the back of our minds that antibiotics are one of the most important breakthroughs in medicine in the 20th century. But bacteria are, and have been for a long time, evolving resistance to them."
Antimicrobial peptides, short protein fragments that punch holes in bacterial membranes, form part of the body's first line of defense. "They can target a broad range of pathogens, and due to their potency, scientists have been trying to synthesize a variety for therapeutic uses," Sil said.
How Did Lactoferrin's Killing Ability Evolve?
Lactoferrin dates to around 160 million years ago, near the end of the Jurassic Period, when the common ancestor of all placental mammals first appeared. The protein's iron-binding function is ancient, but close relatives of lactoferrin lack the bacteria-killing peptide.
That gap suggests the antimicrobial trait appeared after lactoferrin first emerged. By mapping changes in the peptide over millions of years, Barber's team identified when and how that defensive function sharpened.
Could These Peptides Become Medicines?
Not anytime soon, Barber and Sil caution. Peptides are structurally fragile and break down quickly inside the body, unlike conventional antibiotics.
The evolutionary record still offers a natural archive of biological experiments. Barber put it this way: "Evolution is essentially a billions-year-old science experiment, right? We're seeing the results of what worked and what didn't work."
"Looking at how traits are naturally produced and selected through evolution, you can get information that could be useful for designing new antimicrobial tools," he added.
Bacteria can also evolve resistance to antimicrobial peptides, just as they have to antibiotics. By understanding that resistance pathway in advance, researchers may design combination treatments that slow it down.
"If we understand and can anticipate how they become resistant to these molecules," Barber said, "we can hopefully find better ways to target them or develop combination treatments that better avoid resistance."
The study received funding from the National Institutes of Health.
via science.org (Original)
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