Bacteriophage compositions for targeted E. coli lysis

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Solution Overview

Problem

Current methods for controlling pathogenic E. coli strains are inadequate, particularly in human and animal clinical applications, food safety, environmental decontamination, and diagnostics, as they often involve chemical sanitizers that are costly, environmentally harmful, and ineffective against antibiotic-resistant strains.

Innovation Solution

Development of novel bacteriophage compositions, including ECML-1, ECML-10, ECML-123-2, ECML183-2, ECML-359, ECML-363, ECML-606-1, and ECCR-664-1, which have lytic activity against pathogenic E. coli strains, for use in reducing contamination in food products, healthcare facilities, and animal environments, and for enhancing gut resilience.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If chemical sanitizers are used to control pathogenic E. coli, then broad-spectrum antimicrobial activity is achieved, but environmental harm and high cost occur

Engineering Contradiction:
Improveantimicrobial efficacyVSAvoidenvironmental harm
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces chemical sanitizers with bacteriophages, substituting a chemical system with a biological system. Bacteriophages are living viruses that specifically infect and lyse bacterial cells through biological mechanisms rather than chemical action, thereby eliminating environmental contamination from chemical residues while maintaining antimicrobial efficacy.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent introduces bacteriophages as intermediary agents that mediate between the need for antimicrobial control and environmental safety. These phages act as selective mediators that target only pathogenic E. coli strains through specific receptor binding, leaving beneficial microorganisms untouched and avoiding broad-spectrum chemical disruption of environmental ecosystems.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If chemical sanitizers are used to control pathogenic E. coli, then antimicrobial activity is achieved, but high cost occurs

Engineering Contradiction:
Improveantimicrobial efficacyVSAvoidcost
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent employs bacteriophages as disposable, self-replicating agents that can be produced at low cost through simple fermentation processes. Unlike expensive chemical sanitizers requiring continuous purchase and application, phages can be synthesized economically and applied in single-use formulations that maintain efficacy without recurring high costs.

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

Solution Approach 2:

The patent changes the fundamental parameter of antimicrobial agents from chemical compounds to biological entities. This parameter shift enables cost reduction through biological manufacturing methods and eliminates the need for expensive chemical synthesis, purification, and storage infrastructure required for traditional sanitizers.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If broad-spectrum antimicrobials are used, then pathogenic E. coli is controlled, but beneficial microorganisms are also harmed

Engineering Contradiction:
Improvepathogen controlVSAvoiddamage to beneficial microbes
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent applies the principle of local quality by endowing bacteriophages with highly specific host recognition capabilities. Each phage strain is locally optimized to recognize and bind to unique surface receptors on specific pathogenic E. coli strains, creating a targeted action that spares all other microorganisms including beneficial gut flora and environmental microbes.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent inverts the traditional approach by using a biological agent that selectively kills only harmful bacteria rather than a chemical agent that indiscriminately kills all bacteria. This inversion of selectivity—where the 'natural' biological system provides specificity rather than the 'synthetic' chemical system—preserves beneficial microorganisms while controlling pathogens.

Inventive Principle:
Principle #13The other way round (Inversion)

4Reliability

If antibiotics are used to treat E. coli infections, then bacterial growth is inhibited, but antibiotic resistance develops

Engineering Contradiction:
Improveinfection treatmentVSAvoidantibiotic susceptibility
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent replaces antibiotic treatment with bacteriophage therapy, substituting a chemical inhibition mechanism with a biological lysis mechanism. Bacteriophages infect bacterial cells and replicate within them, ultimately causing cell rupture and death through physical lysis rather than chemical inhibition, thereby eliminating the selective pressure that drives antibiotic resistance development.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent introduces bacteriophages as intermediary agents that transfer genetic material between bacteria through transduction, potentially disrupting resistance gene spread. Additionally, phages serve as a natural biological control mechanism that has co-evolved with bacteria for billions of years, providing a sustainable treatment approach that does not contribute to the emerging crisis of antibiotic resistance.

Inventive Principle:
Principle #24Intermediary (Mediator)

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

These bacteriophages effectively reduce pathogenic E. coli colonization and contamination in various settings, including food products and healthcare facilities, while being environmentally friendly and safe for use, and can be administered as pharmaceutical or nutraceutical compositions to modulate the gut microbiome.

Implementation Method 1

Bacteriophages are bacterial viruses that attach to their specific hosts and kill them by internal replication and bacterial lysis involving a complex lytic cycle involving several structural and regulatory genes

Methodology Applied
Scientific EffectLytic cycle:

Data Source

PatentUS20240124851A1Escherichia coli bacteriophages and uses thereof
Publication Date: 2024.04.18 INTRALYTIX INC
  • US20240124851A1 patent drawing
  • US20240124851A1 patent drawing

AI summary

The present invention is directed to isolated bacteriophages having specificity and lytic activity against strains of pathogenic E. coli, methods of using the bacteriophages, progeny and derivatives derived therefrom, to control the growth of pathogenic E. coli in various settings (e.g., food safety, environmental—including food establishments and medical settings—sanitation, urinary tract infections, modulating microbiome, prebiotics, probiotics).