Endolysin Polypeptides Targeting Clostridium perfringens

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Solution Overview

Problem

The increasing antibiotic resistance in Clostridium perfringens strains, particularly Type A, has rendered conventional antibiotics less effective in poultry production, causing diseases like necrotic enteritis and affecting both the pathogen and beneficial bacterial flora, necessitating the development of narrow-spectrum antimicrobials with specific targeting capabilities.

Innovation Solution

Identification and characterization of novel bacteriophage-derived endolysin polypeptides with high specificity and bacteriolytic activity against Clostridium perfringens, including synergistic effects when used in combinations, which can be expressed in host cells like algal cells to enhance their functional properties.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional antibiotics are used to treat C. perfringens infections, then antimicrobial activity is achieved, but antibiotic resistance increases and beneficial flora is damaged

Engineering Contradiction:

Improveantimicrobial activityVSAvoidantibiotic resistance and collateral damage to beneficial flora

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention uses endolysin polypeptides that are specific to C. perfringens cell wall structures, segmenting the antimicrobial action to target only the pathogen without affecting beneficial flora. The endolysins are derived from bacteriophages that specifically infect C. perfringens, providing species-specific and even strain-specific activity.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The endolysin polypeptides exhibit local quality by having specific binding domains that recognize and bind to unique cell wall components of C. perfringens. This localized specificity ensures that the antimicrobial action is confined to the target pathogen while leaving other bacteria unaffected.

Inventive Principle:

Principle #3Local quality

2Adaptability or versatility

If broad-spectrum antibiotics are used, then antimicrobial coverage is increased, but specificity against C. perfringens is reduced and beneficial flora is affected

Engineering Contradiction:

Improveantimicrobial coverageVSAvoidspecificity against C. perfringens

Core Design Contradiction:

Adaptability or versatilityVSManufacturing precision

Solution Approach 1:

The invention segments the antimicrobial spectrum by using endolysins with different specificities. Some endolysins target C. perfringens Type A specifically, while others can target multiple toxin types. This segmentation allows for tailored treatment approaches that provide adequate coverage while maintaining high specificity.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention achieves universality by developing endolysin cocktails where different endolysins with varying specificities work together. This multi-functionality allows the treatment to cover different C. perfringens strains and toxin types while still maintaining overall specificity through the selective combination of endolysins.

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Ease of operation

If single endolysin polypeptides are used, then simplicity of application is maintained, but antimicrobial efficacy is limited

Engineering Contradiction:

Improveapplication simplicityVSAvoidantimicrobial efficacy

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The invention merges multiple endolysin polypeptides into combined formulations or cocktails. These combinations leverage synergistic effects where endolysins with different specificities or mechanisms of action work together to enhance overall antimicrobial efficacy against diverse C. perfringens strains while maintaining relative ease of application.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The endolysin combinations function as composite antimicrobial materials where different polypeptide components with distinct properties are integrated. This composite approach allows the formulation to address multiple aspects of C. perfringens diversity and resistance mechanisms simultaneously.

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

The endolysin polypeptides demonstrate potent antimicrobial activity against Clostridium perfringens, including Type A strains, with enhanced efficacy when used in combinations, minimizing collateral damage to beneficial flora and reducing antibiotic resistance emergence.

Implementation Method 1

Endolysins are used by bacteriophage to degrade the bacterial cell wall peptidoglycans from within the bacteria

Methodology Applied

Scientific EffectEnzymatic hydrolysis: Hydrolysis

Data Source

PatentUS20220290114A1Antimicrobial endolysin polypeptides, compositions and formulations

Publication Date: 2022.09.15 AXITAN HOLDINGS INC

AI summary

The present invention relates to novel endolysin polypeptides or fragments thereof which possess antimicrobial activity, preferably antibacterial activity against Clostridium perfringens. The invention also relates to a nucleic acid molecule encoding the endolysin polypeptide or fragment, a recombinant polynucleotide expression vector comprising such a nucleic acid molecule, as well as a host cell comprising such a nucleic acid molecule or comprising such a recombinant polynucleotide expression vector. The invention also relates to compositions and foodstuffs comprising the endolysin polypeptides or fragments and uses thereof in the treatment of diseases or disorders in animals.