Engineered Microorganism Surface Display for Targeted Pathogen Binding
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Solution Overview
Problem
Current technologies lack effective methods for targeted sensing, detection, or elimination of commensal or pathogenic gut microbes, particularly in the context of engineered microorganisms.
Innovation Solution
Engineered microorganisms, such as Saccharomyces boulardii, are designed to display specific binding agents on their surface, allowing for targeted binding, sensing, or killing of target microorganisms. This is achieved through the use of anchor proteins, transmembrane proteins, and RNA-guided DNA endonucleases like dCas9, which enable precise interaction with target microbes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If engineered microorganisms display binding agents on their surface for targeted binding, then binding specificity to target pathogens is improved, but device complexity increases
Solution Approach 1:
The binding agent is divided into separate functional domains: an extracellular binding domain for pathogen recognition and an intracellular domain for signaling or therapeutic function. This segmentation allows the extracellular portion to maintain high binding specificity while the intracellular portion provides additional functionality without interfering with pathogen recognition.
Solution Approach 2:
A transmembrane anchor protein serves as an intermediary element that connects the extracellular binding domain to the intracellular functional domain. This intermediary structure enables the transmission of binding events from the cell surface to intracellular signaling pathways or therapeutic mechanisms without compromising the binding specificity of the extracellular domain.
2Adaptability or versatility
If multiple binding agents are displayed on the microorganism surface, then versatility in targeting different pathogens is improved, but manufacturing precision requirements increase
Solution Approach 1:
The engineered microorganism is designed with a universal platform architecture that can accommodate multiple different binding agents. Each binding agent uses the same transmembrane anchor and intracellular signaling domain, allowing the system to target multiple different pathogens while maintaining consistent expression and function across different binding specificities.
Solution Approach 2:
Different binding agents are introduced by changing only the extracellular binding domain sequence while keeping other parameters (transmembrane anchor, intracellular domain, promoter elements) constant. This parameter change approach enables versatility in pathogen targeting while simplifying manufacturing control, as only the binding domain needs to be optimized for each specific pathogen.
3Stability of the object's composition
If anchor proteins and transmembrane proteins are used to display binding agents, then binding agent stability on the microorganism surface is improved, but ease of manufacture decreases
Solution Approach 1:
The transmembrane anchor protein and associated signaling components enable the binding agent to be self-assembled and stably maintained on the microorganism surface through its own structural properties. The protein domains automatically localize to the cell membrane and maintain stable display without requiring external stabilization mechanisms or complex manufacturing interventions.
Solution Approach 2:
The binding agent is constructed as a composite protein structure combining extracellular binding domain, transmembrane anchor domain, and intracellular functional domain. This composite architecture provides inherent stability for surface display while the modular nature actually simplifies manufacturing, as each domain can be independently optimized and assembled through standard molecular biology techniques.
Data Source
AI summary
The present disclosure provides for engineered microorganisms and methods of making and using same. The engineered microorganisms as described herein can have a surface display and can be useful as therapeutic agents (e.g., sponges) and biosensors.