Chemostat Phage Evolution for Drug-Resistant Bacterial Strains
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Solution Overview
Problem
Bacteria are evolving resistance to antibiotics faster than new antibiotics are being developed, due to the limitations in the medicine-making process and the mutagenic power of bacteria, necessitating a new approach to combat drug-resistant strains.
Innovation Solution
A system and method, referred to as the Tetrastat, uses a chemostat array culture system to evolve and select bacteriophages that can infect target bacterial strains by maintaining refugee and selection chambers, filtering outflows to isolate and combine phage, and recirculating the phage pool to enhance their mutagenesis and specificity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional antibiotic development processes are used, then new antibiotics can be developed, but the process takes too long (10 years) and costs too much ($1 billion) to keep pace with bacterial resistance evolution
Solution Approach 1:
The patent replaces traditional chemical antibiotic development with a biological system - using bacteriophages (viruses) that naturally infect and kill bacteria. This biological substitution enables rapid evolution and adaptation of phages to target resistant bacterial strains, bypassing the slow chemical development process entirely
Solution Approach 2:
The patent changes the fundamental parameter of treatment from chemical antibiotics to biological phages, and further changes the phage parameters through controlled evolution in chemostat systems. This allows phages to adapt their host range and infectivity properties to match emerging bacterial resistance patterns in real-time
2Object-affected harmful factors
If bacteriophages are used to treat bacterial infections, then targeted killing of bacteria is achieved, but the phages must be continuously adapted to overcome bacterial resistance
Solution Approach 1:
The patent implements self-service by allowing the phage population to automatically adapt to bacterial resistance through controlled evolution in the chemostat system. The phages naturally mutate and select for variants that can infect resistant strains, eliminating the need for complex external adaptation protocols or manual engineering
Solution Approach 2:
The chemostat system provides continuous feedback by maintaining constant interaction between phages and bacteria, allowing real-time selection of effective phage variants. The system monitors bacterial resistance development and automatically selects phages that overcome it, creating a dynamic adaptation loop
3Productivity
If chemostat array culture systems are used to evolve phages, then rapid phage adaptation to target strains is achieved, but the system requires complex filtration and recirculation infrastructure
Solution Approach 1:
The patent applies universality by using identical chemostat apparatus for multiple functions: growing bacteria, evolving phages, filtering outflows, and recirculating phages. The same basic chemostat design serves all evolutionary chambers, reducing the need for specialized equipment for each function
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 Tetrastat system effectively generates bacteriophages that can kill clinically-relevant, drug-resistant bacterial strains, demonstrating rapid development and broad host range efficacy in both laboratory and clinical settings.
Implementation Method 1
filtering outflows from the host chemostat and the target chemostat to isolate phage from the populations of the host bacteria, the target bacteria, and macromolecules
Data Source
AI summary
One aspect of the invention provides a method of generating bacteriophages adapted to infect a target bacterial strain. The method comprises: providing host bacteria that are susceptible to phage as input to a host chemostat containing phage; providing target bacteria that are related to the host bacteria, but not susceptible to phage as input to a target chemostat containing phage; filtering outflows from the host chemostat and the target chemostat to isolate phage from the populations of the host bacteria, the target bacteria, and macromolecules; combining the outflows; and introducing the combined outflow into each of the host chemostat and the target chemostat.