Transduction Particles Targeting B2 E. coli Infections
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Solution Overview
Problem
Current antibiotics are not effective in combating multi-drug resistant B2 phylogroup E coli infections, which are associated with high rates of antibiotic resistance and can be life-threatening, especially in immunocompromised patients.
Innovation Solution
The use of transduction particles that target B2 phylogroup E coli cells with nucleases, specifically encoding CRISPR/Cas systems, which are delivered via adhesion moieties that bind to LPS, LamB, or Tsx on the surface of these cells, effectively killing or inhibiting the growth of the bacteria.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If broad-spectrum antibiotics are used to treat E coli infections, then bacterial growth is inhibited, but beneficial bacteria are killed and microbiome is disturbed
Solution Approach 1:
The invention segments the antibacterial action to target only specific E coli phylogroups (B1, B2, D, F, or G) through phylogroup-specific nucleases delivered by transduction particles, rather than using broad-spectrum antibiotics that affect all bacteria. This selective approach eliminates pathogenic E coli while preserving beneficial bacteria and maintaining microbiome balance.
Solution Approach 2:
The transduction particles are engineered with specific adhesion moieties that bind to phylogroup-specific surface markers on E coli cells, enabling localized and selective delivery of nucleases only to target bacterial populations. This ensures precise action against pathogenic bacteria without affecting other microbial communities.
2Reliability
If conventional antibiotics are used, then bacterial infections are treated, but antibiotic resistance develops
Solution Approach 1:
The invention replaces the chemical mechanism of antibiotics with a biological nuclease-based system that directly cleaves phylogroup-specific genomic DNA. This novel mechanism of action bypasses traditional antibiotic resistance pathways, as the nucleases target specific DNA sequences rather than relying on protein synthesis inhibition or cell wall disruption that bacteria can resist through conventional mechanisms.
Solution Approach 2:
The transduction particles deliver nucleases that recognize and cut specific phylogroup-associated DNA sequences, changing the molecular target from protein-based (antibiotics) to DNA-based (nucleases). This parameter change in the target molecule type eliminates cross-resistance with conventional antibiotics and provides a new therapeutic avenue against resistant strains.
3Object-affected harmful factors
If transduction particles are designed for selective targeting, then beneficial bacteria are preserved, but device complexity increases
Solution Approach 1:
The transduction particle platform is designed as a universal system that can be adapted to target multiple E coli phylogroups (B1, B2, D, F, G) by simply changing the adhesion moiety and nuclease components. This modular multi-functional design allows a single platform to address diverse pathogenic strains while maintaining consistent structural principles, reducing overall system complexity through standardization.
Solution Approach 2:
The adhesion moieties serve as intermediaries that mediate specific recognition between transduction particles and phylogroup-specific surface markers on E coli. This intermediary layer enables selective targeting without requiring complex particle structures, as the adhesion moieties handle the specificity function while the particle core maintains a standardized delivery mechanism.
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
This approach selectively targets and eliminates B2 phylogroup E coli cells, including resistant strains like ST131 and ST1193, without harming beneficial bacteria, thereby providing an effective treatment for potentially life-threatening infections.
Implementation Method 1
each particle comprises an adhesion moiety for recognising and binding to a cognate moiety selected from a LPS, LamB and Tsx displayed on the surface of the phylogroup B2 E coli cells
Implementation Method 2
the nuclease is expressed in the cells and cuts genomic DNA of the cells, thereby killing the cells or reducing growth or proliferation of the cells in the subject
Data Source
AI summary
The invention relates to methods and compositions for treating or preventing an infection by E coli cells in human or animal subjects. The method comprises administering to the subject a plurality of transduction particles that encode a nuclease for targeting the genomes of B2 phylogroup E coli cells.