Multidomain Antimicrobial Polypeptide for Stable Broad-Spectrum Killing
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Solution Overview
Problem
Existing antimicrobial peptides face challenges such as high susceptibility to proteolytic degradation, in vivo toxicity, and high production costs, while nanocarriers for drug delivery are costly and complex to produce, and current fusion proteins lack broad-spectrum antimicrobial efficacy.
Innovation Solution
A recombinant antimicrobial multidomain polypeptide comprising at least three peptidic domains - a non-enzymatic antimicrobial domain, a bacterial binding domain, and an enzymatic antimicrobial domain - is produced in inclusion bodies, offering a one-step process and broad-spectrum antimicrobial effect.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If host defense peptides are used for antimicrobial therapy, then broad-spectrum antimicrobial activity is achieved, but susceptibility to proteolytic degradation and short half-life occur
Solution Approach 1:
The patent combines multiple functional domains into a single multidomain polypeptide: a stabilizing domain (such as albumin or immunoglobulin) merged with antimicrobial peptide domains. This merging protects the antimicrobial domains from proteolytic degradation while maintaining their broad-spectrum activity against both Gram-positive and Gram-negative bacteria.
Solution Approach 2:
The invention creates a composite protein structure where a stable carrier protein (like human serum albumin or immunoglobulin G) is fused with antimicrobial peptide sequences. This composite structure provides both the stability of the carrier protein and the antimicrobial functionality of the peptide domains, resolving the contradiction between activity and stability.
2Reliability
If high doses of host defense peptides are administered, then antimicrobial efficacy is improved, but in vivo toxicity increases
Solution Approach 1:
The multidomain polypeptide merges a pharmacologically safe carrier protein with antimicrobial domains, allowing the active antimicrobial components to be delivered at lower concentrations. The carrier protein acts as a delivery vehicle that reduces off-target effects and systemic toxicity while maintaining efficacy against resistant pathogens.
Solution Approach 2:
The carrier protein serves as an intermediary that mediates the delivery of antimicrobial domains to target sites. This intermediary approach allows controlled release and localized action of the antimicrobial domains, reducing exposure of healthy tissues to toxic concentrations and thereby lowering in vivo toxicity.
3Productivity
If antimicrobial peptides are produced using recombinant technology, then production scalability is improved, but cytotoxicity to producer cells occurs
Solution Approach 1:
The invention merges the antimicrobial peptide domains with a carrier protein domain to create a multidomain polypeptide that is non-toxic to producer cells. This merged structure allows the antimicrobial domains to be expressed at high levels in recombinant systems without killing the host cells, enabling scalable production.
Solution Approach 2:
The carrier protein domain provides preliminary protection against the cytotoxic effects of the antimicrobial domains during production. By pre-combining the antimicrobial sequences with a protective carrier domain, the system prevents self-toxicity that would otherwise occur during high-level expression in producer cells.
4Stability of the object's composition
If nanocarriers are used for drug delivery, then stability and targeted delivery are improved, but production complexity and costs increase
Solution Approach 1:
The invention extracts the essential stabilizing and delivery functions from complex nanocarrier systems and integrates them directly into the polypeptide structure itself. The carrier protein domain within the multidomain polypeptide provides inherent stability and facilitates delivery without requiring separate nanocarrier formulation steps, thereby simplifying production.
Solution Approach 2:
The multidomain polypeptide is self-stabilizing and self-delivering. The carrier protein domain inherently provides structural stability and facilitates cellular uptake or tissue delivery without requiring external nanocarrier systems. This self-service approach eliminates the need for complex two-step production processes involving separate carrier synthesis and encapsulation.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The polypeptide demonstrates enhanced stability, reduced toxicity, and cost-effective production, with a synergistic antimicrobial effect against both Gram-negative and Gram-positive bacteria, including antibiotic-resistant strains, and exhibits antibiofilm activity.
Implementation Method 1
These positively charged peptides have bactericidal broad-spectrum activity since their action is based on their interaction and disruption of negatively charged bacterial cell envelope
Implementation Method 2
the antimicrobial multidomain polypeptide is in form of inclusion bodies (IBs)
Data Source
AI summary
A novel recombinant antimicrobial multidomain polypeptide in an aggregated and functional format is provided. The antimicrobial multidomain polypeptide comprises at least three peptidic domains: a) a non-enzymatic antimicrobial peptidic domain from mammal's immune system, b) a bacterial binding peptidic domain which interacts with the bacterial cell wall or membrane, and c) an enzymatic antimicrobial peptidic domain from mammal's immune system. The antimicrobial multidomain polypeptide exhibits a broad-spectrum antimicrobial effect and is produced in an efficient production system, i.e in form of inclusion bodies.