Health and Medicine
PUBLISHED
Humans need new antibiotics. This fact isn't in dispute. The question of how we find them, however, is much harder to answer.
The idea that a minor infection could morph into an unstoppable, deadly force is unthinkable for most of us. In richer countries at least, there’s barely anyone alive today who remembers a time before antibiotics were readily available.
But the reality of antimicrobial resistance – not just in bacteria, but other microbes too – is that unless new solutions are found, and fast, infections that today seem trivial could easily become killers.
This problem is already here. “Infections that are the most challenging for doctors to treat are becoming increasingly commonplace,” scientists Tomislav Mestrovic and Lucien Swetschinski previously told IFLScience.
Mestrovic and Swetschinski were coauthors of a study that forecast over 39 million deaths from resistant infections between 2025 and 2050 based on data from over 200 countries.
But this grim outlook, they explained, isn't a foregone conclusion: “By increasing global focus on research, drug development, infection prevention, and better patient care [...] we can mitigate the worst outcomes.”
A prehistoric “miracle” protein
A new study from the University of Oregon recently sought inspiration from the far distant past.
Bacteria have been locked in an eternal arms race with animal immune systems since our most ancient ancestors first walked the planet – perhaps, the team reasoned, there are clues buried in prehistoric protein sequences.
“Evolution is essentially a billions-year-old science experiment, right?” said senior author and evolutionary biologist Matt Barber in a statement.
“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.”
The first placental mammals emerged towards the end of the Jurassic Period, some 160 million years ago. With them came lactoferrin, a protein found in breast milk, tears, saliva, and mucus.
Lactoferrin has been called “a miracle molecule.” One of its key functions is to bind iron, holding onto it and keeping it out of reach of marauding bacteria that need it too.
It doesn’t just sit there steadfastly clinging to the iron, though. Lactoferrin has also evolved some active antibacterial defenses of its own, including a peptide – a short protein fragment – that can rupture bacterial cells when it is broken off the main protein sequence.
This peptide, called lactoferricin, is one of a larger class of molecules called antimicrobial peptides (AMPs).
“Antimicrobial peptides are a key 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,” explained first author Titas Sil at the University of Oregon.
How do you revive an ancient protein?
Sil and the team first compared the lactoferrin gene sequences in extant animals, including vampire bats, cows, and humans.
From this, it was possible to infer the most likely evolutionary trajectory of these genes, and the team could make an educated guess at what the lactoferrin gene sequence of these animals’ ancient common ancestors would have been.
The process was pioneered by another University of Oregon scientist, Joseph Thornton, and is called ancestral sequence reconstruction.
Using the gene sequence, the team could then generate actual copies of the ancient protein in cells, thereby “reviving” a protein that existed on Earth 160 million years ago.
They tested its antimicrobial properties and found it wasn’t super effective against major human health threats like Pseudomonas aeruginosa and Streptococcus – the bacteria seemed to be able to get around it.
But the scientists kept going, metaphorically traveling along the family tree, until they reached the likely genetic sequence from mammals dating back just a few million years. Some of these weren't only potently antimicrobial but also outperformed lactoferrin AMPs from modern humans.
The only difference was a single amino acid change, one tiny tweak to the protein’s underlying code.
“What was surprising and unexpected was how small changes in these domains could have such large effects,” said Barber.
“We’re definitely interested in whether by resurrecting or engineering some enhanced antimicrobial peptides, we could use these as therapeutics down the road.”
AMPs: a possible answer to antimicrobial resistance?
The findings are exciting, but it will be some time before we see real clinical results. Compared with the antibiotic drugs we have now, AMPs are less stable and more easily broken down, meaning it’s harder to come up with ways they can be practically used in medicine.
A 2025 study highlighted the potential but also the challenges that AMPs bring.
“[T]ranslating AMPs into effective clinical therapies is a formidable challenge due to issues like nonspecific binding, low solubility, cross-resistance, immunogenicity, susceptibility to proteases, toxicity, and bioavailability,” it read.
“Addressing these challenges requires innovative and interdisciplinary approaches.”
There’s also the issue of bacteria evolving resistance – as they’ve demonstrated, they’re very good at that.
“Similar to antibiotics, pathogens are going to be able to evolve against antimicrobial peptides,” Barber said.
“But if we understand and can anticipate how they become resistant to these molecules, we can hopefully find better ways to target them or develop combination treatments that better avoid resistance.”
Lactoferrin isn't the only protein known to produce potent AMPs. There are also a lot of unanswered questions around AMP biology that scientists are working to understand.
Given the scale of the challenge we face, it’s probably safe to say that any avenues that could lead to new treatments for resistant bacteria are worth exploring.
The study is published in PLOS Biology.
