Chimeric LysM Polypeptides for Gram-Negative Bacterial Lysis

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Solution Overview

Problem

Current antimicrobial treatments are ineffective against antibiotic-resistant Gram-negative bacteria due to their ability to adapt and develop resistance, necessitating new methods to reduce bacterial growth and pathogenicity.

Innovation Solution

Development of antibacterial chimeric polypeptides comprising a LysM segment for traversing the outer membrane of Gram-negative bacteria, combined with muralytic or AntiMicrobial Peptide segments to access the periplasmic space and degrade peptidoglycan, thereby reducing bacterial growth and population.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional antibiotics are used to treat bacterial infections, then bacterial growth is reduced, but antibiotic-resistant bacteria develop and treatment becomes ineffective

Engineering Contradiction:

Improveeffectiveness of antimicrobial treatmentVSAvoidbacterial resistance adaptation

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The invention divides the antibacterial function into two separate segments: (1) a membrane-traversing segment that penetrates the outer membrane of Gram-negative bacteria, and (2) a muralytic segment that degrades peptidoglycan. This segmentation allows each component to be optimized for its specific function while working together to overcome bacterial resistance mechanisms.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention creates a chimeric polypeptide by combining two distinct functional segments (membrane-traversing segment and muralytic segment) into a single composite molecule. This composite structure enables the polypeptide to simultaneously penetrate the outer membrane and degrade peptidoglycan, providing effective antibacterial activity against Gram-negative bacteria including resistant strains.

Inventive Principle:

Principle #40Composite materials

2Reliability

If the outer membrane of Gram-negative bacteria is targeted, then access to periplasmic space is achieved, but the complexity of the bacterial structure makes penetration difficult

Engineering Contradiction:

Improveaccess to periplasmic spaceVSAvoidcomplexity of Gram-negative bacterial structure

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The membrane-traversing segment acts as an intermediary that facilitates penetration through the outer membrane, enabling the muralytic segment to reach its target (peptidoglycan) in the periplasmic space. This intermediary component solves the problem of accessing the periplasmic space by providing a dedicated mechanism for membrane traversal.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Productivity

If chimeric polypeptides are designed to traverse outer membrane and degrade peptidoglycan, then bacterial population is reduced, but the polypeptide structure becomes more complex

Engineering Contradiction:

Improvebacterial population reductionVSAvoidpolypeptide structure

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The invention merges two distinct functional segments (membrane-traversing segment and muralytic segment) into a single chimeric polypeptide molecule. This combining approach allows the polypeptide to perform multiple functions (penetration and degradation) in one structure, achieving effective bacterial population reduction while maintaining a relatively simple overall architecture compared to using multiple separate agents.

Inventive Principle:

Principle #5Merging (Combining)

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 chimeric polypeptides effectively lyse and reduce the population of Gram-negative bacteria, including resistant strains, by traversing the outer membrane and accessing the periplasmic space to degrade peptidoglycan, offering a novel approach to combat antibiotic-resistant infections.

Implementation Method 1

a component for traversing the outer membrane of a Gram-negative bacteria (i.e., a membrane traversing segment)

Methodology Applied

Scientific EffectMembrane traversal:

Implementation Method 2

muralytic segments to access the periplasmic space and degrade peptidoglycan

Methodology Applied

Scientific EffectPeptidoglycan degradation: Enzyme

Data Source

PatentUS11236314B2Chimeric lysm polypeptides

Publication Date: 2022.02.01 BACTOCLEAR HLDG PTE LTD

AI summary

Provided herein are antibacterial compositions and methods of making and using the compositions.