Chimeric Polypeptide Domain Recombination for Bacterial Lysis
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Solution Overview
Problem
The increasing number of antibiotic-resistant bacteria poses a challenge for medicine and healthcare systems, as existing bacteriophage-derived endolysins for treating bacterial infections require high protein doses due to poor stability and activity inhibition in application matrices, and resistance development is a concern.
Innovation Solution
The development of lytic chimeric polypeptides with improved properties through random recombination of cell binding domains and enzymatically active domains, using bacteriophage endolysins, bacteriocins, or bacterial autolysins, to generate and screen for novel chimeric polypeptides with enhanced efficacy and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If bacteriophage-derived endolysins are used to treat bacterial infections, then antimicrobial activity is achieved, but high protein doses are required due to poor stability and activity inhibition in application matrices
Solution Approach 1:
The patent segments the endolysin protein into two functional domains: the cell binding domain (CBD) and the enzymatic active domain (EAD). By separating these domains and creating chimeric polypeptides with optimized combinations, the invention aims to improve stability and reduce the required dosage while maintaining antimicrobial activity.
Solution Approach 2:
The patent creates chimeric polypeptides by combining CBD and EAD domains from different sources into composite structures. These hybrid proteins integrate functional elements to achieve improved stability and reduced dosage requirements compared to wild-type endolysins.
2Speed
If wild-type endolysins are used, then fast onset time is achieved, but resistance development is a concern
Solution Approach 1:
The patent changes the parameters of the endolysin protein by creating chimeric variants with modified domain combinations. This allows optimization of both the fast onset time characteristic and the resistance development issue by selecting domain combinations that maintain rapid activity while reducing resistance risk.
3Adaptability or versatility
If endolysins are used in complex matrices, then therapeutic application is possible, but activity is inhibited
Solution Approach 1:
The patent applies local quality optimization by specifically modifying the CBD domain to enhance binding affinity and stability in complex matrices. By optimizing the local properties of the binding domain while maintaining the catalytic function of the EAD, the chimeric polypeptides achieve both therapeutic applicability and reliable enzymatic activity.
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 method allows for the creation of highly effective lytic chimeric polypeptides that can be used to treat and prevent bacterial infections with potentially lower doses and reduced resistance development, offering a promising alternative to antibiotics.
Implementation Method 1
a catalytic domain that confers the enzymatic activity for hydrolysing specific bonds in the murein or peptidoglycan layer of the bacterial cell wall
Implementation Method 2
a specificity mediating or binding domain that confers binding to a cell surface epitope
Data Source
AI summary
The present invention relates to novel methods of generating and screening for chimeric polypeptides, which can be used in the treatment and prophylaxis of pathogenic bacterial contamination, colonisation and infection. The novel methods are based on random recombination of protein domains, and the chimeric polypeptides obtainable by the methods according to the invention are characterized in that they comprise at least one enzymatic active domain (EAD) and at least one cell binding domain (CBD). The present invention also relates to a library of chimeric polypeptides obtainable by the methods of the present invention.