Ablysin Protein Targeting Peptidoglycan in Drug-Resistant Bacteria
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Solution Overview
Problem
Existing antibacterial proteins are ineffective against multidrug-resistant gram-negative bacteria due to the outer membrane of their cell wall structure, limiting their antimicrobial activity, and there is an urgent need for agents effective against pathogens like carbapenem-resistant Acinetobacter baumannii (CRAB).
Innovation Solution
A recombinant antibacterial protein, Ablysin, with an amino acid sequence represented by SEQ ID NO: 1, targets peptidoglycan in the bacterial cell wall, degrading it to kill multidrug-resistant bacteria including Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecium.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antibacterial proteins are used, then they show killing effect against gram-positive bacteria, but they fail to effectively kill gram-negative bacteria due to the outer membrane barrier
Solution Approach 1:
The patent applies universality by developing an antibacterial protein that can effectively kill both gram-positive and gram-negative bacteria. The protein achieves this by targeting peptidoglycan in the cell wall, which is a common component across both bacterial types, thereby providing broad-spectrum antibacterial activity that overcomes the limitation of conventional proteins being effective only against gram-positive bacteria.
Solution Approach 2:
The patent utilizes parameter changes by modifying the protein's structural and functional characteristics to enable it to penetrate the outer membrane of gram-negative bacteria. This involves altering the protein's properties to allow it to overcome the outer membrane barrier while maintaining its ability to target and degrade peptidoglycan, thus achieving effectiveness against both bacterial types.
2Object-affected harmful factors
If the outer membrane structure of gram-negative bacteria is considered, then it provides a protective barrier, but it prevents the antimicrobial protein from reaching the peptidoglycan layer
Solution Approach 1:
The patent applies the intermediary principle by having the antibacterial protein serve as a mediator that can penetrate the outer membrane barrier. The protein acts as an intermediary substance that overcomes the protective outer membrane structure to reach and degrade the peptidoglycan layer, thereby restoring antimicrobial activity despite the presence of the protective barrier.
Solution Approach 2:
The patent uses parameter changes to modify the protein's properties enabling it to penetrate the outer membrane. By altering the protein's structural and functional parameters, it gains the ability to overcome the outer membrane barrier while maintaining its target specificity for peptidoglycan, thus achieving effective antimicrobial activity against gram-negative bacteria.
3Reliability
If new antimicrobial agents are developed to cope with multidrug-resistant bacteria, then treatment effectiveness improves, but the development process is urgent and complex
Solution Approach 1:
The patent applies self-service by utilizing the bacterial peptidoglycan structure itself as the target and substrate for the antibacterial protein. The protein naturally targets and degrades peptidoglycan, which is an essential component for bacterial cell wall integrity. This self-service approach eliminates the need for complex development processes by leveraging the bacteria's own structural weaknesses against them.
Solution Approach 2:
The patent applies the extraction principle by isolating and utilizing the specific function of peptidoglycan degradation from the complex bacterial cell wall structure. By focusing on extracting and targeting the peptidoglycan component specifically, the patent simplifies the development process while achieving effective treatment against multidrug-resistant bacteria, avoiding the need to address the entire complex cell wall structure.
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
Ablysin effectively kills these bacteria without inducing resistance, making it suitable for pharmaceuticals, disinfectants, food additives, and feed additives, ensuring safety for humans and animals by targeting bacterial-specific substrates.
Implementation Method 1
The Ablysin uses peptidoglycan, which is a component of the cell wall of bacteria, as a substrate, and exhibits bacterial killing ability due to peptidoglycan degradation.
Data Source
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Figure 3~4B
AI summary
The present invention relates to the use of the recombinant antibacterial protein Ablysin for effectively killing multidrug-resistant pathogenic bacteria. The recombinant protein Ablysin of the present invention exhibits apoptosis against antibiotic-resistant Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecium to prevent or treat infectious diseases caused by these bacteria and thus it can be widely used in antibiotics, disinfectants, food additives, feed additives, and the like. In particular, the Ablysin uses peptidoglycan, which is a component of the cell wall of bacteria, as a substrate, and exhibits bacterial killing ability due to peptidoglycan degradation. The peptidoglycan exists only in bacteria and not in humans or animals, and thus there is an advantage that Ablysin of the present invention is safe because it does not affect humans and animals, and can be applied to the pharmaceutical industry, food industry, biotechnology, etc., as well as can effectively kill bacteria in a target place or a target substance without problems of resistance to antimicrobial agents.