Synthetic Peptide Nanonets Could Reduce Inflammatory Responses and Serves as Key Solution in Managing Bacterial Infection, According to Study

Sepsis, commonly called blood poisoning, happens when the body creates an extreme response to infection caused by bacteria, viruses, or fungi. In humans, septic shock is primarily driven by endotoxins from gram-negative bacteria, carrying a 30-50% mortality rate.

In this process, gram-negative bacteria such as Escherichia coli release endotoxins during systemic infections. The inflammatory host's response can cause extensive tissue damage and septic shock if left untreated. These responses are associated with a high mortality rate.

Several attempts have been made by scientists to address this situation, but most of them failed. This is due to the complex communications between anti- and pro-inflammatory mediators. Target-specific approaches in inactivating inflammation mediators are ineffective in improving the prognosis of septic patients in clinical trials. To address this challenge, a multifunctional synthetic peptide nanonet was developed by a group of pharmaceutical scientists from the National University of Singapore (NUS) to alleviate inflammation due to bacterial infection.

New Technique in Managing Infections

Associate Professor Pui Lai Rachel Ee from the Department of Pharmacy started with their hypothesis that synthetic peptide nanonets can effectively lessen inflammatory responses associated with bacterial infections. The anti-inflammatory activity is carried out by the capacity of the nanonets to capture and bind endotoxins released by gram-negative bacteria and inflammation mediators produced by the host macrophages.

In the study by the researchers, the pro-inflammatory cytokines were entrapped selectively by cationic nanonets simultaneously. This allows fine binding of anti-inflammatory cytokines. The scientists successfully exploited the complete difference in the net charge of the two different cytokines groups. The resulting lipopolysaccharide (LPS)-binding effect caused the restoration of colistin's antimicrobial activity, which serves as the last-line therapy of the body against gram-negative bacteria.

The scientists were inspired by the trap-and-kill immune defense approach commonly found in nature. An acute lung injury model in mice demonstrated the intratracheal application of the fibrillating peptides. Aside from the potential to simultaneously trap and kill bacteria, the synthetic peptide nanonets also showed a remarkable ability to act as a complete, multifunctional biomaterial.

The result of this study serves as the first case of multifunctional peptide nanonets with long-ranging effects for use in alleviating the harm of septic complexities at different stages.

Pathogenic Effects of Endotoxin

Endotoxins are substances found in the outer membrane of the cell wall of gram-negative bacteria, acting as a structural and protective layer. This word is synonymous with LPS, although some are not lipopolysaccharides.

Endotoxins are used as an early diagnostic biomarker in detecting bacterial infections caused by gram-negative pathogens. Experts also focus on this chemical due to their vital role in the pharmaceutical and medical industry, particularly in enduring product quality and safety. For instance, injectable drugs must be sterilized to release and kill the endotoxins. Otherwise, they may enter a person's bloodstream and cause fever, shock, and organ failure.

This complex molecule also initiates a host inflammatory response to gram-negative bacterial infection. Enough inflammatory response by mediating clearance of infection and pathogenic toxins likely enhances host survival.