AIEC-Targeted Bacteriophage Strains for Selective Lysis
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Solution Overview
Problem
Current treatments for inflammatory bowel disease (IBD), particularly those targeting adherent-invasive Escherichia coli (AIEC), are ineffective, and there is a need for therapies that can specifically target AIEC without disrupting the healthy human microbiome.
Innovation Solution
Development of bacteriophage strains and compositions comprising these strains that specifically infect and lyse AIEC, including strains ECML-123-2, P2, P8, CLB_P2, ECML-119, ECML-363, and ECML-359, which can be administered in various dosage forms to reduce AIEC colonization and associated diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If broad-spectrum antibiotics are used to treat AIEC infection, then bacterial infection is reduced, but healthy microbiome is disrupted
Solution Approach 1:
The patent divides the treatment approach into specific targeted action (phages against AIEC) rather than broad-spectrum action (antibiotics against all bacteria). Each bacteriophage is engineered to recognize and infect specific AIEC strains through their tail fiber proteins, segmenting the therapeutic effect to affect only the pathogenic bacteria while leaving commensal bacteria untouched.
Solution Approach 2:
The bacteriophages exhibit local quality through their highly specific host range. The patent describes how different phage strains (e.g., ECML-123-2, P2, P8) have been selected and characterized for their specific activity against AIEC strains isolated from IBD patients. This local specificity ensures that the therapeutic action is concentrated on the target pathogen without affecting other bacterial populations in the microbiome.
2Adaptability or versatility
If current IBD treatments are used, then general inflammation is addressed, but AIEC-specific infection is not effectively targeted
Solution Approach 1:
The patent employs a dynamic approach by using living bacteriophages that replicate and propagate within the AIEC population. Rather than static anti-inflammatory drugs, the phages dynamically adapt to the bacterial host, multiplying and lysing AIEC cells throughout the infection site. This dynamic biological system provides both targeted specificity and sustained therapeutic effect.
Solution Approach 2:
The bacteriophages serve as intermediaries between the therapeutic goal (eliminating AIEC) and the biological system (host immune response). The patent describes how phage infection and lysis of AIEC cells may also modulate the host immune response, providing both direct antibacterial effect and indirect anti-inflammatory benefit through the elimination of the pathogenic trigger.
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 bacteriophage strains effectively target AIEC while maintaining a healthy microbiome, providing therapeutic benefits for IBD, urinary tract infections, neonatal meningitis, and respiratory diseases without the side effects of broad-spectrum antibiotics.
Implementation Method 1
Bacteriophages are viruses that infect bacteria and lyse them as part of their replication/lytic cycle
Data Source
AI summary
Described herein are bacteriophages that infect and lyse adherent-invasive Escherichia coli (AIEC). The bacteriophages are useful, for example, for the prophylactic or therapeutic treatment of subjects infected with AIEC or at risk of infection by AIEC, or in the prophylactic or therapeutic treatment of diseases and conditions associated with AIEC, including inflammatory bowel disease (IBD), urinary tract infection (UTI), neonatal meningitis, asthma, chronic obstructive pulmonary disease (COPD), bronchitis, pneumonia, and lung cancer, in a subject in and for other uses described herein.