Pillar[5]arene Quorum-Signal Binding for Host-Cell Protection
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Solution Overview
Problem
Antibiotic resistance in Gram-negative bacteria is exacerbated by the widespread use of antibiotics, and existing methods to inhibit quorum sensing molecules often have toxic effects on human and animal cells, leading to resistance development.
Innovation Solution
Macrocyclic cavity-containing compounds such as pillar[5]arene, resorcin[4]arene, alpha-cyclodextrin, and others bind non-covalently to microbial signaling molecules like N-acyl-homoserine lactones, inhibiting their function without entering cells, thereby reducing virulence and preventing infections.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If conventional methods are used to inhibit quorum sensing molecules, then bacterial virulence is reduced, but toxic effects on human and animal cells occur and resistance development is promoted
Solution Approach 1:
The patent introduces macrocyclic cavity-containing compounds as intermediary substances that bind to quorum sensing molecules. These compounds act as mediators between the bacterial signaling molecules and the host cells, sequestering the virulence factors without directly contacting or toxicly interacting with human or animal cells, thus resolving the contradiction between reducing virulence and avoiding host cell toxicity
Solution Approach 2:
The invention extracts and isolates the harmful quorum sensing molecules from the bacterial system through binding with the macrocyclic compounds. By taking out these signaling molecules from the bacterial communication network, the patent eliminates their virulence effects while leaving the host cells unharmed, as the macrocyclic compounds selectively target the bacterial molecules rather than affecting host cell functions
2Object-affected harmful factors
If conventional methods are used to inhibit quorum sensing molecules, then bacterial virulence is reduced, but resistance development occurs
Solution Approach 1:
The macrocyclic cavity-containing compounds serve as intermediary agents that do not penetrate bacterial cells or human cells. By acting as external mediators that bind to quorum sensing molecules in the environment or on the bacterial surface, they avoid creating selective pressure that would drive resistance development, while still effectively reducing virulence
Solution Approach 2:
The patent employs macrocyclic compounds that can be easily degraded or excreted, similar to disposable objects. These compounds do not persist in the system to create long-term selective pressure for resistance, and their mechanism of action (binding and sequestering) does not involve mechanisms that bacteria can easily counteract through genetic mutation, thus reducing the reliability of resistance development
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 compounds effectively target and neutralize microbial signaling molecules, reducing bacterial virulence without harming human or animal cells and minimizing resistance development, offering a novel approach to combat antibiotic-resistant pathogens.
Implementation Method 1
macrocyclic cavity-containing compounds, such as a resorcin[4]arene, a pillar[5]arene, an alpha-cyclodextrin, a gamma-cyclodextrin, 18-crown-6, 15-crown-5, cucurbit[6]uril and 4-sulfocalix[4]arene, are able to bind non-covalently homoserine lactones
Data Source
AI summary
This invention relates to macrocyclic cavity containing compounds and uses thereof in inhibiting a microbial signalling molecule or in reducing the amount of a microbial signalling molecule in a subject. The invention also relates to methods for inhibiting a microbial signalling molecule or for reducing the amount of a microbial signalling molecule in a subject by contacting a macrocyclic cavity-containing compound with said subject.