Scientists “Resurrect” 160-Million-Year-Old Proteins in Search for New Weapons Against Antibiotic-Resistant Bacteria

American scientists have “resurrected” ancient proteins that existed around 160 million years ago and discovered molecules with natural antimicrobial properties among them. In laboratory experiments, some of these molecules proved more effective than modern counterparts against drug-resistant bacteria. The findings were published in the journal PLOS Biology.

Researchers from the University of Oregon traced the evolutionary history of lactoferrin, an immune-system protein that emerged in the ancestors of placental mammals roughly 160 million years ago, during the Jurassic period. Today, lactoferrin is found in breast milk, tears, saliva, and intestinal mucus, among other places. It binds iron, depriving bacteria of a resource they need to grow and reproduce, and also contains a specific antimicrobial peptide capable of damaging bacterial membranes.

To determine how this antimicrobial ability emerged and changed throughout evolution, the scientists compared lactoferrin gene sequences from modern animals. Using ancestral sequence reconstruction, they then calculated what some of the earliest versions of the protein may have looked like.

The researchers subsequently synthesized the corresponding genes and recreated the ancient proteins in the laboratory. They tested them against several disease-causing bacteria, including Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, and Streptococcus species.

The oldest peptides damaged bacterial membranes, but the microorganisms were able to repair the damage. In later ancestral forms, however, antimicrobial activity gradually became stronger. Some of these proteins even outperformed modern human lactoferrin variants in laboratory tests.

The scientists found that the substantial increase in antimicrobial activity may have been driven by just a single mutation—a small change in the amino acid sequence that makes up the protein.

The researchers believe that studying the evolutionary history of molecules such as these could help scientists develop new treatments for antibiotic-resistant infections. However, practical applications of the ancient peptides are still a long way off. Compared with conventional antibiotics, they are less stable and are rapidly broken down in the body.

Nevertheless, the scientists hope that their findings will help guide the development of new antimicrobial drugs and drug combinations that bacteria, which continually evolve in response to treatment, may find more difficult to evade.