A new constituent sub system of the immune system has been discovered and it is considered as  a source  of potential antibiotics.

Israeli scientists,  revealed  a part of the cell  known to recycle proteins has a secret mode that can germinate an arsenal of bacteria-killing chemicals.

According to them,  it transforms our understanding of human immune system. The cellular waste disposal system called the proteasome is best known for its central role in protein degradation and recycling.

The team discovered that some of the peptides released in the proteasome during protein breakdown are capable of killing bacteria. The researchers found that many of these degradation products matched sequences previously identified as antimicrobial peptides, critical components of the innate immune system, which acts as the body’s first line of defense against bacteria, viruses and parasites

The proteasome is a large protein complex responsible for degradation of intracellular proteins, a process that requires metabolic energy.  The proteasome degrades most cellular proteins in a controlled and tightly regulated manner and thereby controls many processes, including cell cycle, transcription, signalling, trafficking and protein quality control. 

Proteasomal degradation is vital in all cells and organisms, and dysfunction or failure of proteasomal degradation is associated with diverse human diseases, including cancer and neurodegeneration. Target selection is an important and well-established way to control protein degradation.

It is assumed to be a protein “death machine”, destroying a variety of cellular proteins, that have acquired a specific degradation signal(s) such as a multiubiquitin chain. Protein degradation plays a key part in eliciting immune signalling and immune cell differentiation processes.

The proteasome  cleaved antimicrobial peptides (AMPs), contributing to the innate immune response.  AMPs are naturally occurring molecules found in various organisms, including humans, that have a crucial role in the innate immune response against pathogens.

Notably, AMPs are synthesized by a wide range of cells and tissues throughout the body, including epithelial cells, leukocytes and mucosal surfaces, and are present in various body fluids, such as saliva, sweat and tears.

Many AMPs are initially produced as inactive precursors called pro-AMPs, and their activation requires enzymatic processing, often involving proteases. Such AMPs have broad-spectrum antimicrobial activity against bacteria, fungi, viruses and even some parasites.

They work by disrupting microbial cell membranes directly , modulating host transcription and translation . The proteasome-derived peptides provide a cell-autonomous defence mechanism against bacterial infection, collectively termed proteasome-derived defence peptides (PDDPs), are constitutively made, and their production may be enhanced upon bacterial infection, by altering proteasomal composition and function. 

The altered proteasome function is governed by the recruitment of a regulatory subunit of the proteasome, PSME3 within an hour of infection they identified proteasomes with a control unit called PSME3 and found that this subunit was responsible for prioritizing the production of such peptides.

Recent experimental researches shown that, proteasomal-cleaved peptides may be secreted to the extracellular milieu.  The peptide generation rate by proteasomes is at an estimated rate of millions of peptides per minute. Thereby providing the cells with an enormous potential number of protective peptides at a basal state.

This discovery, alongside the established role of proteasome-cleaved peptides in adaptive immunity, positions cellular proteasomes as key orchestrators of what we propose to define as a proteolysis-driven immunity—a dual-function mechanism for immune protection that bridges innate and adaptive immunity.

From an evolutionary perspective, it makes sense that such an extensive system for protein degradation, involving tight regulation, ATP requirements and tens of components, will derive more functions from proteasome-cleaved peptides for cellular defence, offering a previously undescribed model for cellular sustainability.

Natural antibacterials such as PDDPs could provide alternatives to conventional antibiotics in combating antibiotic-resistant infections. Their endogenous production may confer immune tolerance, reducing the risks associated with exogenous AMP treatments.