New class of encrypted peptides offer hope in fight against antibiotic resistance

In a significant advance against the growing threat of antibiotic-resistant bacteria, researchers have identified a novel class of antimicrobial agents known as encrypted peptides, which may expand the immune system's arsenal of tools to fight infection. The findings, published in Trends in Biotechnologyby Cell Press, reveal that many antimicrobial molecules originate from proteins not traditionally associated with immune responses.

Unlike conventional antibiotics that target specific bacterial processes, these newly discovered peptides disrupt the protective membranes surrounding bacterial cells. By inserting themselves into these membranes-much like breaching a fortress wall-the peptides destabilize and ultimately destroy the bacteria.

"Our findings suggest that these previously overlooked molecules could be key players in the immune system's response to infection," says César de la Fuente, presidential assistant professor in bioengineering and in chemical and biomolecular engineering in the School of Engineering and Applied Science, in psychiatry and microbiology in the Perelman School of Medicine,and in chemistry in the School of Arts & Sciences, who led the research team. "This may not only redefine how we understand immunity but also opens up new possibilities for treating drug-resistant infections."

The research team tested the notion that non-immune proteins and peptides are communicating or interacting with the immune system in ways previously unrecognized, contributing to its overall function.

They produced peptides derived from non-immune human proteins and assessed their antimicrobial activity. Remarkably, nearly 90% of these peptides demonstrated significant antimicrobial properties, particularly by disrupting bacterial membranes. Additionally, peptides sourced from the same anatomical regions as the site of infection exhibited enhanced efficacy when used together, indicating potential synergistic effects.

This breakthrough suggests that the immune system leverages a broader toolkit than once thought, opening new avenues for combating antibiotic-resistant infections.

Read more at Penn Medicine News.