Reconstructed ancestral lactoferrin peptides show antibacterial activity in laboratory experiments

University of Oregon researchers used ancestral sequence reconstruction to investigate how lactoferrin-derived antimicrobial peptides evolved and whether ancestral variants could inform antibacterial drug development. The laboratory study, reported in PLOS Biology on August 25, compared gene sequences from living mammals to infer ancestral sequences extending back approximately 160 million years. Reconstructed molecules were tested against pathogens including Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, and Streptococcus.

The oldest reconstructed peptides disrupted bacterial membranes but did not kill the bacteria, which apparently repaired the damage. Variants from more recent mammalian ancestors showed greater antibacterial activity, with some outperforming corresponding modern human peptides, including against drug-resistant bacteria. A single amino acid change was sufficient to substantially enhance activity. The source does not provide numerical potency estimates, experimental sample sizes, or strain-level results.

These findings offer potential starting points for antimicrobial design rather than evidence of clinical efficacy. The researchers caution that these peptides are less structurally stable than conventional antibiotics and are rapidly broken down in the body, limiting near-term therapeutic prospects. Bacteria may also evolve resistance to them. The research was funded by the National Institutes of Health; this account is based on University of Oregon materials summarized by ScienceDaily.