New class of encrypted peptides offers hope in the fight against antibiotic resistance

In a significant advance in the fight against the growing threat of antibiotic-resistant bacteria, researchers have identified a new class of antimicrobial agents known as scrambled peptides that could expand the immune system's arsenal of tools to fight infections. The findingspublished in Trends in biotechnology from Cell Pressshow that many antimicrobial molecules originate from proteins not traditionally associated with immune responses.

Unlike traditional antibiotics that target specific bacterial processes, these newly discovered peptides destroy the protective membranes that surround bacterial cells. By penetrating these membranes – similar to breaking through a fortress wall – the peptides destabilize the bacteria and ultimately destroy them.

“Our results suggest that these previously overlooked molecules may play a key role in the immune system’s response to infection,” he says Cesar de la FuenteAssistant Professor to the President of Bioengineering and of Chemical and Biomolecular Engineering in the Faculty of Engineering and Applied Sciencesin Psychiatry and Microbiology Perelman School of Medicine, and in chemistry School of Arts and Scienceswho headed it Research team. “This could not only redefine our understanding of immunity, but also open up new opportunities for treating drug-resistant infections.”

The research team tested the assumption that non-immune proteins and peptides communicate or interact with the immune system in previously unrecognized ways, contributing to its overall function.

They made peptides derived from non-immune human proteins and evaluated their antimicrobial activity. Notably, almost 90% of these peptides showed significant antimicrobial properties, particularly through disruption of bacterial membranes. Furthermore, peptides derived from the same anatomical regions as the infection site showed increased potency when used together, suggesting possible synergistic effects.

This breakthrough suggests that the immune system uses a broader set of tools than previously thought, opening up new ways to combat antibiotic-resistant infections.

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