Inhibitor Peptides Targeting EspZ Dimerization to Reduce EPEC Virulence
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Solution Overview
Problem
Enteropathogenic Escherichia coli (EPEC) utilizes the EspZ protein to delay host cell apoptosis, facilitating bacterial colonization, and existing methods are inadequate in inhibiting its virulence effectively.
Innovation Solution
Development of inhibitor peptides that target specific regions of the EspZ protein, such as amino acids 37-42 and 75-85, to disrupt its function and reduce virulence by inhibiting dimerization and oligomerization, using a combination of targeting peptides and cell-penetrating peptides to enhance penetration and activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing methods are used to inhibit EspZ function, then bacterial colonization is reduced, but the inhibition is inadequate and virulence persists
Solution Approach 1:
The patent modifies the amino acid sequence of EspZ by substituting residues in the glycine zipper motif (aa75-85) and other critical regions (aa37-42) to create variants with reduced virulence. These parameter changes in the protein sequence specifically impair dimerization and oligomerization while maintaining structural integrity, achieving reliable inhibition of virulence functions.
Solution Approach 2:
The patent extracts and targets the specific functional regions of EspZ, particularly the glycine zipper motif (aa75-85) and transmembrane domains (aa37-42), to develop inhibitor peptides. By focusing on these extracted critical regions, the invention achieves effective disruption of EspZ dimerization and virulence without affecting the entire protein structure.
2Reliability
If inhibitor peptides are designed to target specific amino acid regions, then dimerization is disrupted, but penetration into host cells must be enhanced
Solution Approach 1:
The patent combines two distinct peptide components into a single inhibitor construct: a targeting peptide that specifically binds to EspZ regions (aa37-42 or aa75-85) to disrupt dimerization, and a cell-penetrating peptide (CPP) sequence that facilitates entry into host cells. This merging of functions into one molecule achieves both reliable dimerization disruption and effective cell penetration.
Solution Approach 2:
The cell-penetrating peptide acts as an intermediary that mediates the delivery of the targeting peptide into host cells. The CPP sequence facilitates cellular uptake of the inhibitor construct, enabling the targeting peptide to reach and bind to EspZ at its intended site of action within the cell.
Data Source
AI summary
The present invention features methods, systems, and compositions for inhibiting function of EspZ or an EspZ equivalent, and for inhibiting or reducing virulence of pathogens that utilize EspZ or EspZ equivalent, such as those pathogens that belong to the attaching-effacing (A/E) family. The methods may feature the use of an inhibitor peptide that targets at least a portion of EspZ, such as one of the transmembrane domains. In certain embodiments, the inhibitor peptide disrupts proper dimerization or oligomerization of EspZ.