Science1 publisher2 min readPublished
Reconstructed peptides up to 160 million years old killed resistant bacteria better than some modern versions
University of Oregon biologists revived antimicrobial peptides up to 160 million years old, and some killed drug-resistant bacteria better than modern versions. The lab work suggests evolutionary history is a real source of leads against antibiotic-resistant infections.
The Scientist · Science desk
What happened
- Lactoferrin, the protein at the center of the work, emerged about 160 million years ago near the end of the Jurassic, alongside the first common ancestor of all placental mammals.
- Its main job is to starve bacteria of the iron they depend on, binding the metal tightly enough to keep it out of reach of invading microbes.
- Lactoferrin also carries its own antimicrobial peptide, a protein fragment that tears holes in bacterial membranes and can rupture the cell.
- Lactoferrin's close relatives lack the bacteria-killing ability, so the team concluded the trait arose after lactoferrin appeared and rebuilt ancestral versions to date it.
- The study, from lead author Titas Sil and senior author Matt Barber, was published in the journal PLOS Biology on Aug. 25.
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Why it matters
- capability Reconstructing extinct sequences lets researchers screen defenses evolution already tested, widening the candidate pool for antimicrobial peptides beyond the versions living species happen to carry.
- constraint The evidence supports a method for surfacing leads, not a therapy; the study did not run the toxicity and dosing tests an ancestral peptide would have to clear first.
- precedent Barber's group wants to engineer enhanced peptides from these reconstructions, a repeatable way to generate antimicrobial candidates as resistance keeps spreading.
Titas Sil built the reconstructed peptides by inference. None was ever recovered from a fossil. She lined up lactoferrin gene sequences from living species, including humans and cows, mapped how those sequences are related, and used statistical methods to estimate the most likely gene a shared ancestor carried, pushing the estimate back roughly 160 million years [13]. Peptides are short fragments of proteins, and the reconstruction reaches the earliest placental mammals, a group that includes humans and nearly all mammals alive today [5]. What the team tested is a best statistical guess at an extinct sequence, then synthesized and assayed in the lab.
Barber treats that deep history as usable data. "Evolution is essentially a billions-year-old science experiment, right?" he said [17]. "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." [18]
The result itself is stated narrowly. The release says some reconstructed peptides were more effective against drug-resistant bacteria than some versions found in living species [2]; the study summary sharpens that to more potent than modern human versions [3]. The material does not report how many peptides were tested, which bacteria they faced, or how large the difference was. These were assays against bacterial membranes, not tests in infected animals, so whether an ancestral peptide works at a dose a body can tolerate is still unknown.
Resistance is why the search matters at all; drug-resistant infections are now a major global health challenge [19]. Antimicrobial peptides draw interest because they hit many targets. "Antimicrobial peptides are a key part of the body's first line of defense," Sil said. "They can target a broad range of pathogens, and due to their potency, scientists have been trying to synthesize a variety for therapeutic uses." [16] Barber keeps the horizon distant. "We're definitely interested in whether by resurrecting or engineering some enhanced antimicrobial peptides, we could use these as therapeutics down the road," he said [15]. "But bacteria are, and have been for a long time, evolving resistance to them," Barber said [14].
What to watch
- The PLOS Biology paper itself would give the effect sizes, named pathogens and peptide count.
- Whether any ancestral peptide is tested in infected animals, the step between a membrane assay and a drug candidate.
- Whether Barber's lab moves from reconstructing peptides to engineering enhanced ones, as he said it wants to.