Chimeric Endolysin Lys109 for Antibiotic-Resistant Staphylococcus aureus Control
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current endolysins targeting Staphylococcus aureus face challenges due to high amino acid sequence homology, low genetic diversity, and difficulties in overexpression and solubility in E. coli, limiting the development of effective alternatives to antibiotics for controlling antibiotic-resistant strains and biofilms.
Innovation Solution
Development of chimeric endolysin Lys109 with a novel amino acid sequence, engineered using a random domain-swapping method combining LysSA12 CHAP and LysSA97 amidase domains, which effectively lysing Staphylococcus aureus and its biofilms, including methicillin-resistant strains, and demonstrating enhanced stability and activity in milk.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional endolysins are used to control Staphylococcus aureus, then antibacterial activity is achieved, but high amino acid sequence homology limits genetic diversity and novel development
Solution Approach 1:
The patent combines functional domains from different endolysin sources (LysSA12 CHAP domain with LysSA97 amidase domain) to create a chimeric endolysin Lys109. This merging of domains from distinct bacterial lysins generates novel genetic sequences while preserving antibacterial functionality, directly addressing the limitation of low genetic diversity in traditional endolysins
Solution Approach 2:
The chimeric endolysin Lys109 is constructed as a composite protein molecule integrating functional domains from multiple sources. This composite structure combines the cell-binding domain (CBD) and catalytic domain (CD) in a novel configuration that maintains reliability against S. aureus while introducing genetic versatility through domain recombination
2Productivity
If endolysin is overexpressed in E. coli to increase production, then quantity is improved, but solubility and protein quality deteriorate
Solution Approach 1:
The patent optimizes specific local regions of the endolysin sequence, particularly the CBD and CD domains, to enhance solubility while maintaining expression levels. The chimeric structure incorporates domain configurations that locally improve protein folding and solubility characteristics, allowing successful overexpression in E. coli without sacrificing protein quality
3Reliability
If antibiotics are used to control Staphylococcus aureus, then bacterial growth is inhibited, but antibiotic-resistant strains develop
Solution Approach 1:
The patent replaces the chemical mechanism of antibiotics with a biological mechanism using chimeric endolysin Lys109. This endolysin directly lysesthe peptidoglycan cell wall of S. aureus through enzymatic action, providing a fundamentally different mode of bacterial control that does not select for resistance in the same way antibiotics do, thereby maintaining efficacy while avoiding resistance development
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
Endolysin Lys109 exhibits strong antibacterial activity against a wide range of Staphylococcus aureus, including biofilm removal and effectiveness against antibiotic-resistant strains, offering a promising alternative to traditional antibiotics for treating infections and food safety applications.
Implementation Method 1
an endolysin is an enzyme produced by bacteriophage to destroy the cell wall of peptidoglycan
Implementation Method 2
endolysin Lys109 capable of lysing Staphylococcus aureus and controlling a Staphylococcus aureus biofilm
Data Source
AI summary
The present invention relates to chimeric endolysin Lys109 which effectively controls Staphylococcus aureus, wherein the endolysin Lys109 of the present invention has a novel amino acid sequence that has not been conventionally studied. Endolysin Lys109 of the present invention can be used as a biological regulator capable of effectively inhibiting a wide range of Staphylococcus aureus and a biofilm produced thereby. In addition, endolysin Lys109 can kill Staphylococcus aureus without regard for resistance to conventional antibiotics, and thus can be widely used for treatment of diseases caused by Staphylococcus aureus infection. Moreover, endolysin Lys109 can also be used to resolve medical problems caused by Staphylococcus aureus which has antibiotic resistance.