Engineered Probiotic Microorganisms for Targeted Microcin I47 Delivery

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Solution Overview

Problem

The rise of drug-resistant bacteria, particularly within the Enterobacteriaceae family, poses significant health and economic burdens due to increased morbidity, mortality, and healthcare costs, with limited therapeutic options available.

Innovation Solution

Development of genetically engineered microorganisms capable of producing microcin I47, utilizing a microcin operon and controllable promoters to regulate microcin production, which are delivered as probiotics or in purified form to target and kill drug-resistant bacteria.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional antibiotics are used to treat bacterial infections, then treatment effectiveness is maintained for susceptible bacteria, but drug-resistant bacteria emerge and thrive due to selective pressure

Engineering Contradiction:

Improvetreatment effectivenessVSAvoiddrug resistance

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts the microcin production capability from native bacterial sources and transfers it into engineered probiotic microorganisms through heterologous expression of the microcin operon. This separation allows the therapeutic function (killing drug-resistant bacteria) to be isolated from the problematic selective pressure that drives resistance development, as microcin targets specific bacterial pathways differently than conventional antibiotics

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces engineered probiotic microorganisms as intermediary agents that produce microcin to kill drug-resistant bacteria. These probiotics serve as living factories that deliver the antimicrobial agent directly to the infection site, providing sustained treatment without requiring repeated administration of conventional antibiotics that select for resistance

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If microcin production is continuously high to maximize killing of drug-resistant bacteria, then therapeutic efficacy is improved, but metabolic burden on the engineered microorganism increases and may reduce probiotic viability

Engineering Contradiction:

Improvemicrocin production levelVSAvoidprobiotic viability

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent employs controllable promoters that allow dynamic regulation of microcin operon expression. The promoter can be induced or repressed in response to environmental signals or added inducers, enabling the microorganism to adjust microcin production levels according to therapeutic needs while conserving metabolic resources during non-therapeutic periods, thus maintaining probiotic viability

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The patent changes the expression parameters of the microcin operon by using controllable promoters that respond to specific inducers or environmental conditions. This allows the system to switch between low-expression (maintaining viability) and high-expression (therapeutic killing) states, optimizing both productivity and reliability

Inventive Principle:

Principle #35Parameter changes

3Adaptability or versatility

If a broad-spectrum antimicrobial approach is used to kill various drug-resistant bacteria, then coverage of different pathogens is improved, but harm to beneficial microbiota increases

Engineering Contradiction:

Improvespectrum of bacteria targetedVSAvoiddamage to beneficial microbiota

Core Design Contradiction:

Adaptability or versatilityVSObject-generated harmful factors

Solution Approach 1:

The patent confers specificity to the antimicrobial action by engineering probiotics that produce microcin, which has specific activity against certain Gram-negative bacteria through its mechanism of action on fatty acid synthesis. This localized specificity allows targeting of pathogenic bacteria while sparing beneficial microbiota that are either Gram-positive or have different metabolic pathways, thus maintaining adaptability while reducing harm

Inventive Principle:

Principle #3Local quality

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 engineered microorganisms effectively kill drug-resistant bacteria such as Klebsiella species, reducing infection rates and duration, and offer a novel approach to combatting multidrug-resistant infections.

Implementation Method 1

The controllable promoter controls a level of expression of the one or more microcin genes, thereby controlling the amount of microcin produced by the genetically engineered microorganism

Methodology Applied

Scientific EffectTranscriptional control: Enzyme

Data Source

PatentUS12576128B2Genetically engineered microorganisms and methods of use

Publication Date: 2026.03.17 UNIV OF MASSACHUSETTS

AI summary

This disclosure relates to genetically engineered microorganisms for treating or reducing the risk of bacterial infections or dysbiosis, and further discloses methods of making and using such microorganisms.