Non-pathogenic Bacterium Expressing MAM Polypeptide for Inhibiting Pathogenic Infections
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Solution Overview
Problem
Current methods lack an effective strategy to inhibit pathogenic bacterial infections by targeting a common virulence factor that enables initial host binding across a wide range of pathogens, which is crucial for the activation and secretion of other virulence factors.
Innovation Solution
Administering a composition comprising a non-pathogenic bacterium expressing a MAM polypeptide with multiple mce repeat regions to prevent or inhibit pathogenic bacterial infections, which can be delivered orally or topically and formulated in various forms such as creams, powders, or incorporated into medical devices.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If a common virulence factor is targeted to inhibit pathogenic bacterial infections, then the effectiveness against multiple pathogens is improved, but the ability to establish strong initial host binding is reduced
Solution Approach 1:
The patent uses a non-pathogenic bacterium as an intermediary carrier to deliver the MAM polypeptide to the host. This mediator approach allows the MAM polypeptide to be presented in a controlled manner that maintains host binding capability while providing broad pathogen coverage. The non-pathogenic bacterium serves as a vehicle that can establish initial binding without causing disease, then delivers the antivirulence protein to block pathogenic mechanisms.
Solution Approach 2:
The invention creates a copy of the MAM polypeptide and expresses it in a non-pathogenic bacterium. This copy mechanism allows the therapeutic agent to mimic the structure and function of native MAM proteins from various pathogens, enabling broad-spectrum activity. The copied polypeptide can bind to host cells and deliver antivirulence activity without requiring the presence of actual pathogenic bacteria.
2Reliability
If effector proteins are delivered by secretion systems requiring tight binding, then the activation of virulence factors is improved, but the ease of therapeutic intervention is reduced
Solution Approach 1:
Instead of trying to block the secretion systems or prevent tight binding (which would be difficult), the invention inverts the approach by using a non-pathogenic bacterium to deliver antivirulence proteins that counteract the virulence factors after they are activated. This reverse strategy targets the downstream effects rather than the initial binding event, making therapeutic intervention more feasible.
Solution Approach 2:
The invention converts the pathogenic mechanism of tight binding and effector delivery into a beneficial therapeutic approach. By using a non-pathogenic bacterium that can also establish binding (without causing disease), the same binding mechanism that pathogens exploit is harnessed to deliver protective antivirulence proteins. The harmful tight-binding mechanism is repurposed for therapeutic benefit.
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 approach effectively prevents or inhibits infections by blocking the initial host binding of pathogenic bacteria, reducing cytotoxicity and infection severity across various Gram-negative pathogens.
Implementation Method 1
The approach effectively prevents or inhibits infections by blocking the initial host binding of pathogenic bacteria
Data Source
AI summary
The present invention relates to methods and compositions for preventing or inhibiting pathogenic bacterial infections in a subject caused by pathogenic bacteria expressing a MAM polypeptide by administering to a subject a composition comprising a MAM polypeptide or a non-pathogenic bacterium expressing a MAM polypeptide, or a combination thereof.