Recombinant E.coli zot protein

Zonula Occludens Toxin (ZOT), a protein initially identified in *Vibrio cholerae*, plays a critical role in the pathogenicity of cholera by modulating intestinal epithelial barrier function. Discovered in the 1990s, ZOT selectively increases paracellular permeability of the small intestine by interacting with eukaryotic cell receptors, particularly targeting tight junction complexes. This activity facilitates bacterial dissemination and toxin delivery, contributing to the severe diarrhea characteristic of cholera infection.

Structurally, ZOT contains distinct functional domains: an N-terminal region involved in proteolytic processing, a central receptor-binding domain, and a C-terminal domain critical for toxin secretion. Research revealed that ZOT’s mechanism involves binding to cell surface receptors such as zonulin and epidermal growth factor receptor (EGFR), triggering intracellular signaling cascades that reorganize cytoskeletal proteins (e.g., occludin, ZO-1) and destabilize tight junctions. Interestingly, this property has been repurposed for biomedical applications. Recombinant ZOT, particularly its biologically active fragment ΔG (lacking the N-terminal domain), has emerged as a tool to reversibly enhance epithelial and endothelial permeability. This capability is exploited in drug delivery systems to improve absorption of therapeutics, including macromolecules and nanoparticles, across biological barriers like the blood-brain barrier or intestinal mucosa.

Current studies focus on optimizing ZOT-derived peptides for clinical use, balancing efficacy with safety to avoid unintended immune responses or prolonged barrier disruption. Its potential extends to treating conditions involving excessive barrier integrity, such as inflammatory bowel disease or certain neurological disorders. However, further research is needed to fully elucidate its long-term effects and refine its therapeutic applications.