A Safer Lytic Alternative: Multi-omics and Immunoinformatics Reveal Reduced Inflammatory Impact of a Chimeric Endolysin Against Antibiotic-induced Immune Dysregulation

Atefeh  Noori; Zahra  Amini-Bayat; Saeed  Mirdamadi; Farzaneh  Azizmohseni; Seddigheh  Borhani

doi:10.18502/ijaai.v25i1.20443

Atefeh Noori Department of Biotechnology, Iranian Research Organization for Science and Technology (IROST), Tehran, Iran
Zahra Amini-Bayat Department of Biotechnology, Iranian Research Organization for Science and Technology (IROST), Tehran, Iran
Saeed Mirdamadi Department of Biotechnology, Iranian Research Organization for Science and Technology (IROST), Tehran, Iran
Farzaneh Azizmohseni Department of Biotechnology, Iranian Research Organization for Science and Technology (IROST), Tehran, Iran
Seddigheh Borhani Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

DOI: https://doi.org/10.18502/ijaai.v25i1.20443

Keywords: Antibiotic alternatives; Chimeric endolysin; Cytokine release syndrome; Immune safety; Immunoinformatics; NF-κB

Abstract

Natural killer (NK) cells contribute to the development of Rheumatoid Arthritis (RA). Increased expression of programmed cell death protein 1 (PD-1), encoded by the PDCD1 gene, indicates NK cell exhaustion, a process that may be influenced by microRNAs (miRNAs). In this study, we examined PD-1 expression on NK cells from RA patients and evaluated whether miRNAs modulate this pathway.

Although antibiotics are critical for treating infections, they can provoke harmful immune responses by releasing bacterial components that overstimulate the immune system. Such responses may lead to excessive inflammation or cytokine storms. To address this risk, we assessed the immune safety of a newly designed chimeric endolysin, ZAM-MSC, and compared its effects with traditional antibiotics using transcriptomic, proteomic, and computational analyses.

We analyzed public gene and protein expression datasets from antibiotic-treated human cells and performed in silico studies on ZAM-MSC. Differential expression analysis and pathway enrichment were conducted, alongside structural modeling of the endolysin and its predicted interactions with immune receptors.

Antibiotic treatment strongly activated inflammatory genes and pathways, including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK). In contrast, ZAM-MSC minimally affected immune-related gene expression, with downregulation of interleukin-6 receptor (IL6R) and tumor necrosis factor receptor 1A (TNFRSF1A). Structural modeling showed weak interactions with Toll-like receptors, and epitope analysis predicted low immunogenicity. These results suggest ZAM-MSC may offer a safer antimicrobial alternative, though all protein-level findings are based on computational predictions and require experimental validation.