Bacteriophage Panels for C. difficile Infection Treatment
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Solution Overview
Problem
The limited availability of effective bacteriophages specifically targeting Clostridium difficile (C. diff) strains, coupled with the challenges of isolating and characterizing phages that are non-toxic to humans while being effective against C. difficile, hinders the development of effective phage-based therapies for treating C. difficile infections, which are increasingly resistant to conventional antibiotics.
Innovation Solution
Identification and characterization of 7 novel bacteriophages (NCTC 12081404 to 12081410) capable of killing C. difficile, with detailed ribotype specificity and deposition under the Budapest Treaty, forming panels that can be used alone or in combination for therapeutic applications, including the option of additional components like antibiotics or carriers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antibiotics are used to treat C. difficile infections, then treatment is available, but antibiotic resistance is developing
Solution Approach 1:
The patent transitions from using small molecule antibiotics to using bacteriophage viruses as the therapeutic agent. This fundamental parameter change in the type of antimicrobial agent being used allows treatment of C. difficile infections while avoiding the development of antibiotic resistance, as phages infect bacteria through specific receptor recognition rather than disrupting cellular metabolism like antibiotics
Solution Approach 2:
The patent replaces the chemical mechanism of antibiotics with the biological mechanism of bacteriophage infection. Instead of using chemical compounds that inhibit bacterial growth, the invention uses living viruses that specifically infect and lyse C. difficile bacteria, providing an alternative therapeutic mechanism that bypasses antibiotic resistance
2Adaptability or versatility
If bacteriophages are used to treat C. difficile infections, then targeted therapy is provided, but isolation and characterization of suitable phages is difficult
Solution Approach 1:
The patent performs preliminary enrichment of environmental samples to concentrate bacteriophages that infect C. difficile before attempting isolation and characterization. This preliminary action increases the likelihood of successfully isolating suitable phages by pre-concentrating them from complex environmental matrices
Solution Approach 2:
The patent uses C. difficile strains as intermediary hosts to propagate and characterize the isolated bacteriophages. These intermediary bacterial cultures serve as a bridge between the environmental sample and the final therapeutic phage product, allowing for characterization of phage host range and infectivity
3Quantity of substance
If C. difficile phages are isolated from clinical samples, then phages are obtained, but the ribotype specificity has not been characterised and only 5 phages were found
Solution Approach 1:
The patent isolates and characterizes bacteriophages from environmental soil samples rather than clinical samples, expanding the source beyond a single location type. This universal approach to sampling multiple environmental sources increases the diversity of phages isolated and allows for broader ribotype specificity characterization across different C. difficile strains
Solution Approach 2:
The patent systematically characterizes the ribotype specificity of each isolated phage against multiple C. difficile ribotypes, using the characterization data to inform further isolation and selection efforts. This feedback loop ensures comprehensive understanding of each phage's host range and guides the development of effective phage cocktails
4Device complexity
If a single bacteriophage is used, then simplicity is maintained, but broad host range coverage is limited
Solution Approach 1:
The patent combines multiple bacteriophages with different ribotype specificities into phage cocktail formulations. By merging several phages that target different C. difficile ribotypes, the therapy achieves broad host range coverage while maintaining relative simplicity in administration as a single combined formulation
Solution Approach 2:
The patent segments the C. difficile ribotype population into different groups targeted by specific phages, then combines these segmented phage preparations into comprehensive cocktails. This segmentation approach allows systematic coverage of diverse ribotypes while organizing the complexity into manageable phage groups
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 demonstrate broad host range efficacy, capable of killing multiple C. difficile ribotypes, including 027 and 014/020, and have shown therapeutic utility both in vitro and in vivo, providing a promising alternative to traditional antibiotics by effectively reducing C. difficile colonization and infection.
Implementation Method 1
Bacteriophages (also called phages) are viruses that specifically infect bacteria
Data Source
AI summary
The present invention relates to a panel of bacteriophage, wherein the panel comprise any one or more bacteriophage selected from the group consisting of:—NCTC 12081404, NCTC 12081405, NCTC 12081406, NCTC 12081407, NCTC 12081408, NCTC 12081409 and NCTC 12081410. The invention also relates to the use of such panels for treating C. difficile infection, or for prophylactic treatment of subjects not yet colonized by C. difficile or that have been colonized but the colonization has not yet progressed to infection.