Lactobacillus acidophilus SlpA Protein Modulating Inflammatory Responses
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Solution Overview
Problem
Current therapies for inflammatory bowel disease (IBD) and other inflammatory conditions often have undesirable side effects, such as depleting beneficial intestinal microflora and increasing the risk of infection and cancer, highlighting the need for new therapeutic agents that can modulate immune responses without global immune suppression.
Innovation Solution
A recombinant Lactobacillus acidophilus bacterium genetically modified to decrease or eliminate the display of lipoteichoic acid (LTA), surface layer protein B (SlpB), and surface layer protein X (SlpX), with the recombinant bacterium or purified surface layer protein A (SlpA) administered to subjects to treat inflammation-mediated diseases, including IBD, by promoting regulatory immune responses and intestinal homeostasis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If current therapies for IBD are used, then inflammatory responses are suppressed, but beneficial intestinal microflora are depleted and risk of infection and cancer increases
Solution Approach 1:
The patent extracts and isolates the specific therapeutic component SlpA from the Lactobacillus acidophilus bacterium. By purifying and administering only the SlpA protein rather than whole bacteria or broad-spectrum immune suppressants, the therapy achieves anti-inflammatory effects while avoiding the harmful side effects of depleting beneficial microflora and increasing infection risk.
Solution Approach 2:
SlpA acts as an intermediary molecule that mediates between the gut microbiota and the host immune system. It specifically binds to SIGNR3 receptors on dendritic cells and macrophages to modulate immune responses, providing a targeted mechanism that avoids global immune suppression and protects beneficial microflora while treating inflammation.
2Object-affected harmful factors
If Lactobacillus acidophilus is used to treat inflammatory diseases, then regulatory immune responses are promoted, but unwanted immune activation may occur
Solution Approach 1:
The patent applies local quality by modifying the Lactobacillus acidophilus strain to have differential surface properties - eliminating LTA and specific Slp variants while retaining SlpA. This creates localized differences in immune interaction, where SlpA specifically promotes regulatory responses through SIGNR3 binding while the absence of other surface components prevents unwanted immune activation.
Solution Approach 2:
The patent changes the surface composition parameters of Lactobacillus acidophilus by genetically modifying it to eliminate LTA and certain Slp proteins. This parameter change in surface molecule composition selectively alters immune system interactions to favor regulatory responses while avoiding pathogenic activation, achieving anti-inflammatory effects without unwanted immune activation.
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 modified Lactobacillus acidophilus strain and SlpA effectively reduce inflammation, protect intestinal barrier function, and prevent dysbiosis, demonstrating therapeutic efficacy in murine models of colitis and other inflammatory conditions by inducing regulatory immune responses and maintaining gut microbiota balance.
Implementation Method 1
CLECs recognize carbohydrate structures on self and non-self antigens... DC-SIGN, which was previously shown to bind L. acidophilus-SlpA in vitro... is a calcium-dependent carbohydrate-binding protein with specificity for the mannose-containing glycans of microbial surface components
Implementation Method 2
The gastrointestinal (GI) microbiota plays a critical role in determining the immunologic outcome of various signaling events in host cells... the composition of the GI microbiota and host immunity are mutualistic and continuously influence each other
Data Source
AI summary
The current invention provides a recombinant bacterium, the recombinant bacterium being genetically modified to decrease or eliminate the display of lipoteichoic acid (LTA), surface layer protein B (SlpB) and surface layer protein X (SlpX) on the surface of said bacterium. Efficacious therapies for a subject suffering from an inflammation mediated disease are also provided. The methods of the current invention comprise administering to a subject in need thereof a therapeutically effective amount of the recombinant L. acidophilus cells or a therapeutically effective amount of the isolated surface layer protein A (SlpA) or a non-naturally occurring derivative thereof. The recombinant L. acidophilus cells or SlpA isolated from L. acidophilus can be in a pharmaceutical composition comprising a pharmaceutically acceptable carrier and/or excipient. In an embodiment of the invention, the pharmaceutical composition is administered orally.