Macrocyclic Cavity Compounds Sensitize Bacteria to Antibiotics

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Solution Overview

Problem

The rapid buildup of antibiotic resistance in bacteria, particularly in pathogens like Pseudomonas aeruginosa, renders existing antibiotics ineffective, leading to a significant global health crisis with limited new antibiotic classes being developed in the past 35 years, threatening to make antibiotic-resistant infections the deadliest cause by 2050.

Innovation Solution

The use of macrocyclic cavity-containing compounds, such as pillar[5]arene, which bind microbial signaling molecules and interact with the bacterial outer membrane, sensitizing bacteria to antimicrobial agents, reducing the required dosage, prolonging antibiotic effectiveness, and inhibiting biofilm formation, thereby reducing resistance development and enhancing antibiotic efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If antibiotics are used to treat bacterial infections, then the growth of bacteria is inhibited, but bacteria rapidly develop resistance rendering the antibiotics ineffective

Engineering Contradiction:

Improveantibiotic efficacyVSAvoidduration of antibiotic effectiveness

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The macrocyclic compound is administered before the antibiotic to pre-sensitize the bacteria by disrupting their membrane and signaling systems, making them more vulnerable to the subsequent antibiotic treatment and delaying resistance development

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The macrocyclic compound acts as an intermediary that modifies the bacterial state, making them more susceptible to antibiotics by disrupting their outer membrane and quorum sensing mechanisms, thereby enhancing antibiotic penetration and effectiveness

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If high doses of antibiotics are administered to overcome resistance, then bacterial growth is suppressed, but the build-up of resistance accelerates

Engineering Contradiction:

Improvebacterial growth suppressionVSAvoidresistance build-up

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The macrocyclic compound changes the physiological parameters of the bacteria (membrane permeability, signaling activity) making them susceptible to lower antibiotic doses, thereby achieving effective bacterial suppression without selecting for high-level resistance

Inventive Principle:

Principle #35Parameter changes

3Reliability

If frequent administration of antibiotics is performed to maintain effective levels, then bacterial infections are controlled, but the administration interval must be shortened

Engineering Contradiction:

Improveinfection controlVSAvoidadministration interval

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The macrocyclic compound is given in advance to prime the bacterial population, extending the window of susceptibility and allowing longer intervals between antibiotic administrations while maintaining infection control

Inventive Principle:

Principle #10Preliminary action

4Reliability

If antibiotics are used to treat infections, then pathogenic microbes are killed, but the amount of antibiotic needed increases over time

Engineering Contradiction:

Improvemicrobe eliminationVSAvoidantibiotic dosage

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The treatment uses a composite approach combining the macrocyclic compound with antibiotics, where the macrocyclic agent enhances the penetration and effectiveness of the antibiotic, reducing the total quantity of antibiotic needed to achieve microbe elimination

Inventive Principle:

Principle #40Composite materials

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 makes resistant bacteria susceptible to antimicrobial agents again, reduces the amount of antibiotics needed, delays resistance development, and inhibits biofilm formation, offering a synergistic effect with various antibiotic classes and reducing the global rise of antibiotic resistance.

Implementation Method 1

The macrocyclic cavity-containing compound inhibits a microbial signalling molecule or reduces the amount of a microbial signalling molecule by binding the microbial signalling molecule by non-covalent host-guest bonding

Methodology Applied

Scientific EffectHost-guest interaction: Absorption (physical)

Implementation Method 2

binding the microbial signalling molecule by non-covalent host-guest bonding

Methodology Applied

Scientific EffectNon-covalent binding: Absorption (physical)

Data Source

PatentUS20230145342A1Combinatory treatment

Publication Date: 2023.05.11 ARIVIN THERAPEUTICS OY

AI summary

This invention relates to use of a macrocyclic cavity-containing compound sensitizing a microbe towards an antimicrobial agent. The invention also relates to use of a macrocyclic cavity-containing compound in reducing the amount of an antimicrobial agent needed to prevent or inhibit the growth of a microbe in a subject. Further, the invention relates to use of a macrocyclic cavity-containing compound in reducing the build-up of resistance of a microbe towards an anti-microbial agent. The invention also relates to a macrocyclic cavity-containing compound and an antimicrobial agent for use in inhibiting/treating/preventing a microbial infection in a subject having a microbial infection or being at risk of a microbial infection.