Engineered Antimicrobial Peptides for Antibiotic-Resistant Bacteria

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Solution Overview

Problem

The increasing problem of antibiotic-resistant bacteria, particularly in the Enterobacteriaceae family, poses a significant threat to food safety and human health due to the misuse of antibiotics in animal agriculture, leading to contamination of the food supply and potential transfer of resistance genes to human pathogens.

Innovation Solution

Development of engineered antimicrobial peptides, such as those with specific amino acid sequences (e.g., SEQ ID NOs: 1-11), which are effective against Gram-negative bacteria like Enterobacteriaceae, including Escherichia coli and Klebsiella pneumoniae, by interacting with bacterial membranes to inhibit growth or kill these pathogens.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If antibiotics are used to prevent disease and promote growth in food animals, then animal health and productivity are improved, but antibiotic-resistant bacteria develop and contaminate the food supply

Engineering Contradiction:

Improveanimal health and productivityVSAvoidfood safety

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent employs antimicrobial peptides as a replacement for long-lasting antibiotics. These peptides are designed to be effective against bacteria but do not promote resistance in the same way conventional antibiotics do, thereby maintaining food safety without the harmful side effects of antibiotic overuse in animal agriculture

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent modifies the chemical structure and properties of antimicrobial peptides to enhance their effectiveness against antibiotic-resistant bacteria. By changing parameters such as peptide sequence, charge distribution, and structural conformation, the invention creates peptides that can overcome bacterial resistance mechanisms while maintaining safety

Inventive Principle:

Principle #35Parameter changes

2Reliability

If conventional antibiotics are used to treat bacterial infections, then infection is controlled, but resistance genes are transferred to human pathogens

Engineering Contradiction:

Improveinfection controlVSAvoidresistance gene transfer

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces antimicrobial peptides as an intermediary substance that eliminates bacteria without promoting resistance gene transfer. These peptides act as a bridge solution between infection control needs and the prevention of resistance dissemination, targeting bacterial cell membranes directly without the selective pressure that drives resistance evolution

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent converts the harmful effect of bacterial resistance into a benefit by designing peptides that specifically target and disrupt resistant bacteria. The peptides are engineered to recognize and bind to specific bacterial membrane characteristics, turning the resistance problem into a targeted therapeutic advantage

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

3Productivity

If antimicrobial peptides are designed to be highly effective against bacteria, then bacterial killing efficiency is improved, but toxicity to human cells may increase

Engineering Contradiction:

Improvebacterial killing efficiencyVSAvoidcytotoxicity

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by designing peptides with specific regional properties that target bacterial membranes while sparing human cells. The peptide structure includes distinct functional regions: positively charged domains for bacterial membrane binding, hydrophobic regions for membrane insertion, and terminal groups that enhance selectivity. This localized action ensures high bacterial killing efficiency without compromising human cell safety

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent utilizes dynamics by creating peptides that can change their structural conformation in response to environmental cues. The peptides adopt different shapes and charges depending on whether they are in aqueous solution or interacting with bacterial membranes, allowing them to activate only when needed and maintain safety in human biological environments

Inventive Principle:

Principle #15Dynamics

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 peptides demonstrate high efficacy in reducing viable bacterial numbers, with some strains showing over 2-3 order of magnitude reduction in colony formation, and are effective against antibiotic-resistant strains and biofilms, while maintaining low toxicity to human cells.

Implementation Method 1

Cathelicidins interact with the membranes of susceptible bacteria, form higher order structures to cause ion leakage and the death of the bacteria

Methodology Applied

Scientific EffectIon leakage:

Implementation Method 2

Cathelicidins could also bind bacterial cell wall materials, including lipopolysaccharide (LPS) molecules that are potent inducers of the inflammatory responses

Methodology Applied

Scientific EffectBinding:

Data Source

PatentUS11793858B2Bactericidal peptides and uses thereof

Publication Date: 2023.10.24 INDIANA UNIVERSITY RESEARCH & TECHNOLOGY CORP

AI summary

Antimicrobial compositions having bactericidal activity are described. Also described is a method of treating bacterial infections using compositions comprising antimicrobial peptides or variants thereof.