Ancient mammal proteins show power against superbugs

Scientists have brought back versions of germ-fighting proteins from the dawn of placental mammals, about 160 million years ago, and found that some of them work better against drug-resistant bacteria than their modern human equivalents.

The research, from the University of Oregon, was published in the journal PLOS Biology. It was led by doctoral student Titas Sil, with evolutionary biologist Matt Barber as senior author.

Reconstructing the past

The team focused on lactoferrin, a protein found in milk, saliva and other body fluids that helps defend against infection. By comparing lactoferrin genes across living species and mapping how they are related, the researchers estimated what the protein looked like in ancient ancestors. The technique, called ancestral sequence reconstruction, was pioneered by Joseph Thornton, formerly of the University of Oregon.

They then made the predicted genes, produced the ancient proteins in the laboratory and tested them against bacteria linked to human disease.

Better than today's version

Some of the ancient antimicrobial peptides outperformed modern human versions against drug-resistant pathogens including Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli and Streptococcus species. Much of the improvement came down to a single change in one amino acid, one of the building blocks of proteins.

"What was surprising was how small changes in these domains could have such large effects," Barber said.

Not a medicine yet

The researchers stress that the peptides are unstable and break down quickly in the body, so they are not ready to be used as treatments. But the work shows that evolution's past experiments could offer new starting points in the search for antibiotics.

That search is urgent. Antimicrobial resistance, where bacteria evolve to survive the drugs designed to kill them, is one of the biggest threats to modern medicine, and few new classes of antibiotic have been discovered in recent decades. The study was funded by the National Institutes of Health.