Phage-Derived Endolysin Lytic Agent for Selective Enterococcus Control
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Solution Overview
Problem
Current methods for treating acute graft-versus-host disease, such as antibiotics and fecal microbiota transplantation, are ineffective in targeting Enterococcus faecalis and disrupt the intestinal bacterial flora, leading to increased mortality and lack a safe standard treatment.
Innovation Solution
A lytic agent comprising a phage-derived endolysin enzyme with specific amino acid sequences or active fragments is developed to selectively lyse Enterococcus faecalis, preserving beneficial bacteria and restoring intestinal flora balance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If antibiotics are administered to kill Enterococcus bacteria, then the bacterial load is reduced, but beneficial bacteria are also killed and intestinal flora configuration cannot be restored
Solution Approach 1:
The patent segments the bacterial population by targeting only Enterococcus species through phage-specific endolysins, while leaving other beneficial bacteria unaffected. This selective segmentation allows reduction of harmful bacteria without disrupting the overall intestinal flora configuration.
Solution Approach 2:
The invention applies local quality by using phage-derived endolysins that are specifically active against Enterococcus cell walls. The lytic activity is localized to the target pathogen through phage specificity, unlike broad-spectrum antibiotics that affect all bacteria.
2Stability of the object's composition
If fecal microbiota transplantation is performed to improve intestinal bacterial flora, then beneficial bacteria are introduced, but donor-derived drug-resistant-bacterial infection risk increases
Solution Approach 1:
The patent extracts and utilizes phage-derived endolysins from the bacterial genome itself, separating the therapeutic agent from the need for fecal transplantation. This extraction approach eliminates the risk of introducing donor-derived pathogens while maintaining the ability to restore intestinal flora by selectively eliminating Enterococcus.
3Reliability
If broad-spectrum antibiotics are used to treat enterococcal infection, then Enterococcus faecalis is killed, but the method lacks therapeutic efficacy in restoring intestinal flora
Solution Approach 1:
The patent introduces phage-derived endolysins as intermediary agents that mediate the elimination of Enterococcus faecalis. These endolysins act as selective mediators that target the cell wall of Enterococcus without affecting beneficial bacteria, thereby achieving therapeutic efficacy while preserving intestinal flora.
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 lytic agent enhances survival rates in model mice with graft-versus-host disease by effectively targeting and lysing Enterococcus faecalis, reducing dysbiosis and associated infections without harmful side effects.
Implementation Method 1
a lytic agent for Enterococcus faecalis, consisting of a lytic enzyme comprising any of the amino acid sequences of the following (a) to (c) or an active fragment thereof
Implementation Method 2
Whole-genome analyses have been performed on a total of 11 isolates. As a result, a prophage sequence in the genome of the isolates and an endolysin gene in the prophage sequence have been found
Data Source
AI summary
A lytic agent for Enterococcus bacteria which includes a lytic enzyme or an active fragment thereof is provided. The lytic enzyme includes (a) the amino acid sequence shown in SEQ ID NO: 1, (b) an amino acid sequence in which one or multiple amino acids are added, deleted, and/or substituted in the amino acid sequence shown in SEQ ID NO: 1, or (c) an amino acid sequence having a sequence identity of 90% or more with the amino acid sequence shown in SEQ ID NO: 1.