Mutant Bacteriophage Host-Range Expansion via Serial Passaging
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Solution Overview
Problem
Current bacteriophages are too specific to each bacterial type, making them ineffective against real-world infections and contamination, and the development of phage cocktails is complex and challenging.
Innovation Solution
A method to produce mutant bacteriophages with expanded host-range by repeatedly passing selected phage strains through cultures containing varying ratios of their natural host and a target host, followed by purification and screening to isolate phages that infect the target host, and then propagating these mutants in the target host to create a stock of mutant phages.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If bacteriophages are used to target specific bacterial strains, then they can effectively eliminate that particular bacteria, but they are too specific to be useful against real-world infections or contamination involving multiple bacterial types
Solution Approach 1:
The patent applies parameter changes by mutagenizing the bacteriophage genome to alter its host-range parameters. Through exposure to mutagens and repeated passaging, the phage's genetic parameters are changed to enable infection of multiple bacterial species while maintaining effectiveness against the original target strain
Solution Approach 2:
The patent achieves universality by creating mutant bacteriophages that can infect multiple bacterial species (universal host-range) while maintaining their lytic function. The resulting phages serve multiple purposes: treating specific infections, preventing contamination, and providing broad-spectrum antimicrobial activity
2Adaptability or versatility
If phage cocktails containing multiple variants are created to combat specific bacterial strains, then broader coverage is achieved, but the process of searching for, isolating, and propagating specific phage strains becomes complex and challenging
Solution Approach 1:
The patent applies self-service by allowing the bacteriophage population to undergo natural mutation and selection processes when exposed to mutagens and repeated passaging. The system self-generates diversity and selects for phages with expanded host-range capabilities, eliminating the need for complex manual screening and isolation of multiple specific strains
Solution Approach 2:
The patent applies preliminary action by pre-mutagenizing the phage population and performing repeated passaging before final application. This preliminary evolution step creates a diverse phage population with expanded host-range, simplifying subsequent selection and application processes
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 resulting mutant phages are more infectious to their natural host and can infect a second host, allowing for broader bacterial coverage and increased efficacy against diverse bacterial variants, potentially replacing antibiotics in human health and industry applications.
Implementation Method 1
A bacteriophage (phage) is a virus that infects and replicates within a bacterium
Implementation Method 2
Viruses are known to undergo mutation very quickly and even retain mutations which cause them to infect bacteria other than their established host
Data Source
AI summary
A method of producing novel bacteriophages with expanded host-range and bacteriophages with expanded host ranges are disclosed. The method produces mutant phage strains which are infectious to a second host and can be more infectious to their natural host than in their natural state. The method includes repeatedly passaging a selected phage strain into bacterial cultures that contain varied ratios of its natural host bacterial strain with a bacterial strain that the phage of interest is unable to infect; the target-host. After each passage the resulting phage are purified and screened for activity against the target-host via double-overlay assays. When mutant phages that are shown to infect the target-host are discovered, they are further propagated in culture that contains only the target-host to produce a stock of the resulting mutant phage.