Charged Compounds Disrupt Biofilm Structural Components

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Solution Overview

Problem

Current therapeutic approaches are inadequate for inhibiting biofilm formation and reducing or eliminating biofilms, particularly in conditions like cystic fibrosis, where persistent Pseudomonas aeruginosa infections are challenging due to biofilm formation facilitated by neutrophils and their-derived DNA and F-actin.

Innovation Solution

Administering charged compounds, such as polyamino acids, to interfere with the structural components of biofilms, either directly to patients or to medical devices, to prevent or disrupt biofilm formation, including the use of polyaspartic acid, polyglutamic acid, polyarginine, and protease inhibitors to target neutrophil activity and biofilm structure.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If antibiotics and host defense mechanisms are used to eradicate P. aeruginosa infection, then initial success in eradicating environmental strains occurs, but persistent infection becomes inevitable due to biofilm formation

Engineering Contradiction:
Improveinfection eradicationVSAvoidinfection longevity
Core Design Contradiction:
ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent applies preliminary action by administering charged compounds (polyamino acids, polynucleotides, peptide nucleic acids) before or during early stages of biofilm formation to prevent the development of persistent infections. These compounds interfere with the structural components of biofilms (DNA, F-actin) before they can establish chronic infections that resist conventional antibiotics

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses charged compounds as intermediary substances that mediate between the host defense system and the bacterial biofilm. These compounds specifically target and disrupt the structural framework of biofilms (particularly DNA and F-actin components) without relying solely on conventional antibiotics, thereby enabling eradication of persistent infections

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If neutrophils accumulate to fight infection, then host defense response is activated, but biofilm formation is facilitated by neutrophil-derived DNA and F-actin

Engineering Contradiction:
Improvehost defense effectivenessVSAvoidbiofilm formation
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent converts the harmful effect of neutrophil-derived DNA and F-actin (which facilitate biofilm formation) into a target for therapeutic intervention. By using charged compounds that specifically bind to and disrupt DNA and F-actin structures, the treatment exploits the very components released by neutrophils during their anti-bacterial activity, thereby preventing these components from serving as building blocks for biofilms

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

Solution Approach 2:

The charged compounds act as intermediaries that specifically target the interface between neutrophil activity and biofilm formation. These compounds bind to DNA and F-actin released by neutrophils, preventing their incorporation into biofilm structures while allowing neutrophils to continue their antimicrobial functions

Inventive Principle:
Principle #24Intermediary (Mediator)

3Quantity of substance

If conventional antibiotics are used to treat infection, then bacterial growth is inhibited, but biofilm structure protects bacteria from antibiotic eradication

Engineering Contradiction:
Improvebacterial loadVSAvoidinfection clearance
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent applies segmentation by separating the treatment approach into two distinct mechanisms: (1) conventional antibiotics that reduce bacterial load by inhibiting growth, and (2) charged compounds that disrupt the biofilm structural framework (DNA, F-actin). This segmentation allows each component to address a different aspect of the infection, with the charged compounds penetrating the biofilm barrier that protects bacteria from antibiotics

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent employs a composite therapeutic approach combining conventional antibiotics with charged compounds (polyamino acids, polynucleotides, or peptide nucleic acids). This composite strategy leverages the bactericidal activity of antibiotics against planktonic bacteria while the charged compounds simultaneously dismantle the biofilm matrix, thereby achieving complete infection clearance that neither approach could achieve alone

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 charged compounds effectively disrupt and prevent biofilm formation by interacting with DNA and F-actin, reducing the longevity and severity of infections by inhibiting biofilm establishment and enhancing the effectiveness of antibiotics.

Implementation Method 1

The charged compounds effectively disrupt and prevent biofilm formation by interacting with DNA and F-actin

Methodology Applied
Scientific EffectElectrostatic interaction: Electrostatics

Data Source

PatentUS9314479B2Methods and compositions for the disruption of biofilms
Publication Date: 2016.04.19 NAT JEWISH HEALTH
  • US9314479B2 patent drawing
  • US9314479B2 patent drawing
  • US9314479B2 patent drawing

AI summary

The invention relates to methods of inhibiting biofilm formation or reducing biofilms in a subject or on a device or surface by administering a charged compound such as a polyamino acid to a subject, device or surface. The invention also relates to compositions for inhibiting biofilm formation or reducing biofilms.