Bacteriophage ΦCJ13 ETEC Control Antibiotic Resistance

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Solution Overview

Problem

The misuse and overuse of broad-spectrum antibiotics have led to antibiotic-resistant bacteria and residue issues in livestock, necessitating a specific bactericidal agent effective against Enterotoxigenic E.coli (ETEC) that is also acid- and heat-resistant.

Innovation Solution

A novel bacteriophage, ΦCJ13, specifically targeting ETEC with bactericidal activity, is isolated and used in compositions for prevention and treatment of ETEC-related diseases in livestock, including feed additives, sanitizers, and cleaners, maintaining stability across various pH and temperature conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If broad-spectrum antibiotics are used to treat E.coli infections, then bacterial growth is inhibited, but antibiotic resistance and drug residue problems arise

Engineering Contradiction:
Improveeffectiveness against E.coliVSAvoidantibiotic resistance and drug residue
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and utilizes a specific bacteriophage (ΦCJ13) that targets only ETEC bacteria, eliminating the need for broad-spectrum antibiotics. This selective approach kills ETEC through lytic infection while leaving other bacteria unaffected, thus preventing antibiotic resistance and residue accumulation in livestock and environment

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The bacteriophage ΦCJ13 acts as a biological intermediary that mediates the killing of ETEC bacteria. Instead of using chemical antibiotics that cause resistance, the patent employs this viral intermediary that naturally infects and lyses ETEC cells, providing an alternative mechanism that avoids harmful side effects

Inventive Principle:
Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If bacteriophage with specific target spectrum is used, then antibiotic resistance is avoided, but effectiveness against diverse E.coli strains is limited

Engineering Contradiction:
Improveantibiotic resistanceVSAvoideffectiveness against diverse E.coli strains
Core Design Contradiction:
Object-affected harmful factorsVSAdaptability or versatility

Solution Approach 1:

The patent modifies and optimizes the bacteriophage ΦCJ13 through controlled infection conditions and formulation parameters to enhance its lytic efficiency against ETEC. By adjusting parameters such as multiplicity of infection, incubation time, and environmental conditions (pH, temperature), the bacteriophage maintains high effectiveness while preserving its strain-specific targeting capability

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs a dynamic approach by using bacteriophage that can adapt and replicate within the host ETEC population. The self-replicating nature of the bacteriophage allows it to dynamically increase its concentration at the infection site, ensuring effective control of ETEC without requiring broad-spectrum activity against all E.coli strains

Inventive Principle:
Principle #15Dynamics

3Reliability

If bacteriophage is used in gastrointestinal tract, then ETEC is controlled, but acid resistance is required for survival

Engineering Contradiction:
ImproveETEC control in gastrointestinal tractVSAvoidacid resistance at low pH
Core Design Contradiction:
ReliabilityVSTemperature

Solution Approach 1:

The patent applies preliminary protective measures by formulating the bacteriophage ΦCJ13 with acid-resistant carriers or protective matrices that shield the virus from gastric acid during passage through the stomach. This preliminary protection ensures the bacteriophage remains viable when it reaches the intestinal tract where ETEC infection occurs

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent utilizes the short-lived but highly effective nature of bacteriophage particles that are administered in sufficient quantities to overcome acid degradation. Even though individual phage particles may be damaged by acid, the large dosage ensures enough viable particles reach the intestine to effectively control ETEC infection

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

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

ΦCJ13 effectively inhibits ETEC growth, reducing disease symptoms and antibiotic resistance, and can be used in diverse applications such as feed additives and sanitizers without inducing drug tolerance, addressing the limitations of conventional antibiotics.

Implementation Method 1

bacteriophage is a specialized type of virus that infects only particular bacteria and controls the growth of bacteria, and can self-replicate only inside host bacteria

Methodology Applied
Scientific EffectBacteriophage infection and lysis:

Implementation Method 2

the bacteriophage has a specific bactericidal activity against pathogenic E.coli, in addition to excellent acid- and heat-resistance

Methodology Applied
Scientific EffectAcid resistance:

Implementation Method 3

the bacteriophage has a specific bactericidal activity against pathogenic E.coli, in addition to excellent acid- and heat-resistance

Methodology Applied
Scientific EffectHeat resistance:

Data Source

PatentEP2780447B1Novel isolated bacteriophage having e. coli-specific bactericidal activity and antibacterial composition comprising the same
Publication Date: 2018.01.10 CJ CHEILJEDANG CORP
  • EP2780447B1 patent drawingFigure 1~2
  • EP2780447B1 patent drawingFigure 3~4
  • EP2780447B1 patent drawingFigure 5~6

AI summary

The present invention relates to a novel bacteriophage having an E.coli-specific bactericidal activity, a composition for the prevention or treatment of infectious diseases caused by Enterotoxigenic E.coli comprising the bacteriophage as an active ingredient, an antibiotic comprising the bacteriophage as an active ingredient, a feed additive composition comprising the bacteriophage as an active ingredient, a sanitizer or cleaner comprising the bacteriophage as an active ingredient, and a method for treating colibacillosis using the bacteriophage. The novel bacteriophage of the present invention has a specific bactericidal activity against pathogenic E.coli, and excellent acid- and heat-resistance. Therefore, the novel bacteriophage can be used for the prevention or treatment of swine colibacillosis, which is an infectious disease caused by pathogenic E.coli, and can also be widely used in animal feed additive compositions, sanitizers, and cleaners.