Interfering Agents Target HU Protein Biofilm Disruption

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Solution Overview

Problem

Current methods fail to effectively target and disrupt bacterial biofilms, particularly those formed by pathogens like P. gingivalis, due to the immune system's inability to recognize and neutralize the DNABII family of proteins, leading to persistent infections and biofilm-related issues in both human and industrial settings.

Innovation Solution

Development of specific interfering agents that target and inhibit the HU polypeptide's binding to microbial DNA, using modified antibodies that recognize and bind to mutated HU polypeptides, thereby disrupting biofilm structure and preventing bacterial infection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If the immune system and antibiotics are used to treat bacterial infections, then common infections can be cleared, but chronic and recurrent infections persist due to bacteria hiding in biofilms

Engineering Contradiction:
Improveinfection clearance effectivenessVSAvoidbiofilm protection
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and targets the specific HU protein component from within the biofilm structure. By developing interfering agents that specifically bind to HU proteins, the invention removes the protective function of this key biofilm component, making bacteria vulnerable to immune system and antibiotics even when embedded in biofilms.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces interfering agents as intermediary molecules that mediate between the immune system/antibiotics and the protected bacteria. These agents specifically bind to HU proteins in the biofilm matrix, disrupting the biofilm structure and enabling immune cells and antibiotics to access and eliminate the bacteria.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Stability of the object's composition

If DNABII proteins are targeted to disrupt biofilm structure, then biofilm stability is compromised, but the immune system fails to produce neutralizing antibodies against these proteins

Engineering Contradiction:
Improvebiofilm structure stabilityVSAvoidimmune neutralization capability
Core Design Contradiction:
Stability of the object's compositionVSReliability

Solution Approach 1:

The patent creates synthetic interfering agents that replicate the binding capability of hypothetical neutralizing antibodies. Instead of relying on the immune system to produce antibodies against DNABII proteins, the invention synthesizes molecules that copy and enhance the desired binding interaction, providing reliable disruption of biofilm structure without depending on immune response.

Inventive Principle:
Principle #26Copying

3Object-affected harmful factors

If bacteria invade host cells to persist, then they are protected from immune system and antimicrobials, but they eventually kill host cells and cause chronic infection

Engineering Contradiction:
Improvebacterial protectionVSAvoidinfection chronicity
Core Design Contradiction:
Object-affected harmful factorsVSDuration of action of stationary object

Solution Approach 1:

The patent applies preliminary anti-action by targeting and disrupting biofilm structures before bacteria can establish protected intracellular infections. By interfering with HU protein function and destabilizing biofilms in advance, the invention prevents bacteria from using biofilms as a springboard for cell invasion and chronic infection establishment.

Inventive Principle:
Principle #9Preliminary anti-action

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 solution effectively inhibits biofilm formation and prevents bacterial infection by specifically targeting the HU polypeptide, making bacteria susceptible to the immune system and antimicrobials, thus addressing the persistence of chronic infections and biofilm-related problems.

Implementation Method 1

an interfering agent that competes, titrates or inhibits binding of an HU polypeptide to a microbial DNA

Methodology Applied
Scientific EffectCompetition binding:

Implementation Method 2

modified antibodies that recognize and bind to mutated HU polypeptides

Methodology Applied
Scientific EffectAntibody-antigen binding:

Data Source

PatentUS11690892B2HU specific interfering agents
Publication Date: 2023.07.04 RES INST AT NATIONWIDE CHILDRENS HOSPITAL
  • US11690892B2 patent drawing
  • US11690892B2 patent drawing
  • US11690892B2 patent drawing

AI summary

Methods of and compositions for breaking down a biofilm or inhibiting, preventing or treating a microbial infection that produces a biofilm are disclosed, which involves administration of an interfering agent capable of specifically competing, titrating, or inhibiting the binding of an HU protein to a microbial DNA. By competing with HU proteins that bind to DNA scaffold in the biofilm, these interfering agents destabilize the biofilm leading to destruction and removal of the biofilm by the immune system. Further method and composition aspects are contemplated in relation to infections caused by bacteria that export an HU protein.