Carbohydrate-Binding Modules Block Pathogen Attachment
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Solution Overview
Problem
Current treatments for diseases caused by pathogens, such as influenza and bacterial respiratory pathogens, often involve enzymatic removal of cell surface carbohydrates, which can expose cryptic receptors to other pathogens, making cells vulnerable to infection, and may elicit an immune response.
Innovation Solution
The use of carbohydrate-binding modules (CBMs), particularly family 40 CBMs, to block pathogens' access to cell surface carbohydrates, preventing colonization and infection without removing the carbohydrates, thereby avoiding the risks associated with enzymatic treatments and immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If enzymatic removal of cell surface carbohydrates is used to treat pathogens, then pathogen binding is inhibited, but cryptic receptors are exposed making cells vulnerable to other pathogens
Solution Approach 1:
The invention extracts and utilizes only the carbohydrate-binding module (CBM) from the complete sialidase enzyme, separating the binding function from the enzymatic hydrolysis function. This allows selective blocking of pathogen binding to sialic acid receptors without removing the sialic acid residues, thereby preventing pathogen attachment while maintaining cell surface integrity and avoiding exposure of cryptic receptors
Solution Approach 2:
The CBM acts as an intermediary molecule that competitively binds to sialic acid receptors on cell surfaces, preventing direct interaction between pathogens and their receptors. This mediator approach blocks pathogen attachment without altering the cell surface carbohydrate structure, avoiding the harmful effect of exposing cryptic receptors while maintaining normal cell function
2Reliability
If enzymatic removal of cell surface carbohydrates is used, then pathogen colonization is prevented, but immune response is elicited
Solution Approach 1:
The invention isolates the carbohydrate-binding module from the complete sialidase enzyme, retaining only the non-catalytic binding domain. This extracted CBM provides pathogen binding inhibition without the enzymatic activity that would remove sialic acid and trigger immune responses, thereby preventing colonization while avoiding immune system activation
Solution Approach 2:
The CBM creates a protective copy or mimic of the natural sialic acid-binding interaction that pathogens exploit. By providing synthetic CBM molecules that bind to the same receptors, the invention creates a decoy system that satisfies pathogen binding requirements without involving actual enzymatic modification of cell surface carbohydrates, thus preventing colonization while avoiding immune detection
3Reliability
If multivalent lectins are used to bind sialic acid, then binding affinity is increased, but complexity of the molecule increases
Solution Approach 1:
The invention segments the complete sialidase enzyme into separate functional modules, isolating only the carbohydrate-binding module (CBM) with approximately 160 amino acids. This segmentation creates a simplified, single-domain protein that provides effective sialic acid binding without the complexity of the full enzymatic structure, achieving high binding affinity through the dedicated CBM domain while maintaining molecular simplicity
Solution Approach 2:
The invention extracts the essential binding function from the complex sialidase enzyme by removing the catalytic domain and accessory modules, retaining only the ~160 amino acid CBM. This extraction achieves effective sialic acid binding with a simplified molecular structure, providing high binding affinity through the isolated CBM while avoiding the complexity of the complete enzyme system
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 CBMs effectively prevent pathogens from binding to cell surface carbohydrates, reducing the risk of infection and providing a targeted approach to treating diseases like influenza and bacterial respiratory infections without exposing cells to additional vulnerabilities.
Implementation Method 1
Sialic acid recognition is mediated via lectins or lectin-like molecules and their corresponding receptors... bind to their receptor with relatively high affinity due to the multivalent nature of these molecules
Implementation Method 2
CBMs are found widely in glycoside hydrolases and are discrete, non-catalytic modules that primarily exist to target the parent enzyme to its substrate for efficient hydrolysis by increasing the concentration of the enzyme at the substrate surface
Implementation Method 3
Sialidases, or neuraminidases, catalyze the hydrolysis of sialic acids from a variety of glycoconjugates
Data Source
Figure 1A~1B
Figure 2A~2D
Figure 3A~3B
AI summary
The present invention provides compounds, compositions, medicaments and methods comprising or using carbohydrate binding molecules. More specifically, the invention provides a means of treating diseases and/or conditions caused or contributed to by pathogens, particularly microbial pathogens and methods of screening, identifying, detecting tagging and/or labelling carbohydrates.