Autotransporter-binding molecules inhibit bacterial aggregation

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Solution Overview

Problem

Current treatments for biofilm-associated infections are often ineffective due to the shielding effect of biofilms, which protect bacteria from antibiotics and host immune factors, and there is a need for compositions and methods to reduce bacterial aggregation and biofilm formation.

Innovation Solution

Development of autotransporter-binding molecules that inhibit bacterial aggregation and biofilm formation by blocking the interactions between autotransporter proteins, specifically using antibodies or antigen binding fragments that target specific sequences of autotransporter proteins such as Ag43a, thereby preventing homodimerization and attachment to surfaces.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If antibiotics and host immune factors are used to treat bacterial infections, then bacterial killing is achieved, but biofilms shield bacteria making treatments ineffective

Engineering Contradiction:
Improveeffectiveness of antibiotic treatmentVSAvoidshielding effect of biofilm
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by using autotransporter-binding molecules to prevent biofilm formation and bacterial aggregation before antibiotic treatment is administered. The binding molecules block autotransporter-mediated aggregation pathways, keeping bacteria in a planktonic state that is susceptible to conventional antibiotics, thereby making subsequent antibiotic treatment effective where it would otherwise fail.

Inventive Principle:
Principle #10Preliminary action

2Stability of the object's composition

If autotransporter proteins are allowed to interact freely, then bacterial aggregation and biofilm formation occur, but this protects bacteria from antibiotics and immune factors

Engineering Contradiction:
Improvebiofilm structureVSAvoidresistance to antibiotics and immune factors
Core Design Contradiction:
Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent employs an intermediary approach by introducing autotransporter-binding molecules that specifically bind to autotransporter proteins and block their aggregation function. These binding molecules act as intermediaries that interfere with the autotransporter-protein interactions necessary for biofilm formation, thereby disrupting biofilm structure and eliminating the protective shielding effect without directly killing the bacteria.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If surgical removal of infected tissue is performed, then biofilm-associated infections are treated, but this is invasive and does not address the underlying aggregation mechanism

Engineering Contradiction:
Improveinfection clearanceVSAvoidsurgical intervention
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies self-service by enabling the host's immune system to effectively clear infections through the action of autotransporter-binding molecules. These molecules enhance the susceptibility of bacteria to host defenses by preventing biofilm formation, allowing the immune system to perform its natural function without requiring invasive surgical intervention. The treatment leverages the body's own defense mechanisms rather than imposing external surgical solutions.

Inventive Principle:
Principle #25Self-service

Data Source

PatentUS11897941B2Compositions and methods for reducing bacterial aggregation
Publication Date: 2024.02.13 THE UNIVERSITY OF QUEENSLAND
  • US11897941B2 patent drawing
  • US11897941B2 patent drawing
  • US11897941B2 patent drawing

AI summary

The present disclosure relates to compositions and methods for inhibiting bacterial aggregation, and in particular, to compositions and methods that inhibit autotransporter-mediated bacterial aggregation or attachment. Described herein are autotransporter binding molecules such as antibodies and antigen binding fragments thereof. The autotransporter binding molecules block self-association between autotransporters and autotransporter-mediated surface attachment.