Chimeric endolysin ZAM-MSC shows minimal inflammatory gene activation compared to traditional antibiotics in computational models.

Traditional antibiotics are crucial for treating bacterial infections, but their mechanism of action can lead to the release of bacterial components that overstimulate the host immune system. This overstimulation can trigger excessive inflammation or even dangerous cytokine storms, posing a significant risk to patient safety. There is a critical need for novel antimicrobial agents that can effectively combat infections without provoking harmful immune responses. This study explores the immune safety profile of a new chimeric endolysin, ZAM-MSC, as a potentially safer alternative to conventional antibiotics.

Researchers assessed the immune safety of a newly designed chimeric endolysin, ZAM-MSC, by comparing its predicted effects with traditional antibiotics using transcriptomic, proteomic, and computational analyses. They analyzed public gene and protein expression datasets derived from antibiotic-treated human cells. For ZAM-MSC, in silico studies were performed, involving differential expression analysis, pathway enrichment, structural modeling of the endolysin, and prediction of its interactions with immune receptors. Epitope analysis was also conducted to predict its immunogenicity.

Antibiotic treatment consistently demonstrated strong activation of inflammatory genes and pathways, specifically including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK). In stark contrast, ZAM-MSC minimally affected immune-related gene expression. The computational analysis revealed downregulation of interleukin-6 receptor (IL6R) and tumor necrosis factor receptor 1A (TNFRSF1A) in response to ZAM-MSC. Structural modeling further indicated weak interactions between ZAM-MSC and Toll-like receptors.