Researchers have discovered a new class of antimicrobial compounds called encrypted peptides, which could boost the immune system's toolkit to combat infection and counteract the growing problem of antibiotic-resistant bacteria.
The research, which was published by Cell Press in the journal Trends in Biotechnology, showed that a large number of antimicrobial compounds come from proteins that are not often linked to immune responses.
These recently identified peptides interfere with the protective membranes that enclose bacterial cells, in contrast to traditional antibiotics that target particular bacterial activities. The peptides enter these membranes, destabilizing and eventually killing the bacteria, much like breaking through a fortress wall.
Our findings suggest that these previously overlooked molecules could be key players in the immune system’s response to infection. This may not only redefine how we understand immunity but also open up new possibilities for treating drug-resistant infections.”
César de la Fuente, Presidential Associate Professor and Research Lead, Penn Medicine
Expanding the Scope of Immunity
It has long been believed that proteins specifically connected to immune processes are the main source of support for the immune system. The immune system produces unique proteins called immune proteins, often known as antibodies, to identify and fight against invaders like bacteria and viruses.
Nevertheless, the latest study shows that structural proteins also support antimicrobial defenses, as do structural proteins found in the neurological and visual systems. This increased dependence on a variety of proteins points to a more complex and adaptable immune response than was previously thought.
The research team developed what they refer to as the “Cross-talk Hypothesis” to investigate the idea that non-immune proteins and peptides are engaging or talking with the immune system in ways that were previously unknown, thereby supporting the immune system's overall function.
They synthesized peptides from human non-immune proteins and evaluated their antibacterial efficacy. Surprisingly, almost 90% of these peptides showed notable antibacterial activity, especially through bacterial membrane disruption. Furthermore, when combined, peptides from the same anatomical locations as the infection site demonstrated increased potency, suggesting possible synergistic effects.
This discovery implies that the immune system uses a wider range of tools than previously believed, creating new opportunities to fight illnesses resistant to antibiotics.
Promising Preclinical Results
Eight of the produced peptides had strong anti-infective action in mouse models, which resulted in a marked reduction in bacterial infections. In addition to their antibacterial activities, these peptides demonstrated immunomodulatory qualities, which alter or control the immune system's reaction and impact significant inflammatory mediators that are essential for the body's reaction to infections.
A New Approach in the Fight Against Antibiotic Resistance
The timing of the discovery is crucial. Over 1.3 million deaths occur each year due to the emergence of antibiotic-resistant bacteria, which poses a serious threat to global health. By 2050, it is estimated that up to 39 million people will have died from antibiotic-resistant diseases.
Researchers want to create treatments that are less likely to develop resistance and more effective by utilizing the body's natural defenses through these non-immune proteins.
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