Host-Targeting Bacterial Uptake Assay for Antibiotic Resistance
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Solution Overview
Problem
The rise of antibiotic resistance has created a gap in the availability of effective antimicrobials, necessitating alternative therapies that can target host cells rather than pathogens to circumvent resistance.
Innovation Solution
Methods are described for analyzing drugs and molecules to enhance or inhibit the uptake of pathogenic bacteria by host cells, using compounds like thiamylal and colistin to treat antibiotic-resistant infections, and quantifying intracellular bacteria using a CFU-less assay.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antibiotics are used to treat bacterial infections, then bacterial growth is inhibited, but antibiotic resistance develops
Solution Approach 1:
Instead of targeting the bacteria directly with antibiotics, the invention inverts the approach by targeting the host cell's uptake mechanisms. Host-targeting compounds modulate the host cell to either enhance or inhibit bacterial internalization, thereby treating infection without directly confronting the pathogen and avoiding the selection pressure that drives antibiotic resistance.
Solution Approach 2:
The invention introduces host-targeting compounds as intermediaries that act on the host cell rather than directly on the bacteria. These compounds modulate host cell functions (such as uptake mechanisms) to control bacterial internalization, using the host cell as a mediator to achieve therapeutic effect while circumventing direct pathogen-targeting and the associated resistance problem.
2Reliability
If new antibiotics are developed to overcome resistance, then treatment effectiveness improves, but development cost and time increase
Solution Approach 1:
Host-targeting compounds have the potential to be universally effective against multiple types of bacteria, including antibiotic-resistant strains. By targeting conserved host cell mechanisms rather than specific bacterial targets, a single host-targeting compound may address diverse pathogens, reducing the need for pathogen-specific drug development and accelerating therapeutic availability.
Solution Approach 2:
The invention performs preliminary action by modulating host cell uptake mechanisms before bacterial infection establishes itself. By enhancing or inhibiting bacterial internalization at the host cell level, the treatment prevents infection progression without requiring complex pathogen-specific mechanisms, thereby simplifying development and reducing time to therapy.
3Adaptability or versatility
If host-targeting compounds are used to modulate bacterial uptake, then antibiotic resistance is circumvented, but understanding of uptake mechanisms is required
Solution Approach 1:
The invention employs self-service by using the host cell's own uptake mechanisms against the pathogen. Host-targeting compounds leverage the host cell's natural internalization pathways, turning the host's physiology into the therapeutic tool. This approach simplifies the therapeutic strategy by utilizing existing biological systems rather than requiring complex external delivery mechanisms.
Data Source
AI summary
CFU-less assays of quantifying intracellular bacteria and methods of using the CFU-less assays to identify host-targeting modulators of pathogen uptake or killing by host cells are described. Also described are host-targeting modulators of pathogen uptake by host cells and methods of using the host-targeting modulators to treat infection