Lactobacillus paracasei MCC1849 Resists Enzymatic Degradation

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Solution Overview

Problem

Lactic acid bacteria with high IL-12 production-inducing ability are often compromised by cell wall-digesting enzymes and RNases in the human body, leading to reduced immunostimulatory effects.

Innovation Solution

A novel strain of Lactobacillus paracasei MCC1849, which exhibits high IL-12 production-promoting activity and maintains this activity even after treatment with cell wall-digesting enzymes or RNases, is identified and used in drugs, foods, and feeds to enhance immune response and provide antivirus benefits.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If lactic acid bacteria are used to induce IL-12 production and enhance immunity, then prophylactic and defensive actions against infections are improved, but the bacteria's activity is reduced by cell wall-digesting enzymes and RNases in the human body

Engineering Contradiction:
Improveimmunostimulatory effectVSAvoidenzymatic degradation
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies this principle by discovering that certain lactic acid bacteria strains produce RNase-resistant RNA molecules that can withstand degradation. Instead of trying to protect the bacteria from enzymatic attack, the invention converts the harmful enzymatic environment into a selective advantage, where only bacteria producing resistant RNA survive and maintain their immunostimulatory function. This is achieved by identifying strains like Lactobacillus paracasei MCC1849 that naturally produce such resistant RNA.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent applies parameter changes by modifying the chemical structure of RNA molecules through bacterial production to increase their resistance to RNase degradation. The bacteria alter the physical-chemical parameters of the RNA (such as methylation patterns or sequence composition) to create molecules that are less susceptible to enzymatic cleavage, thereby maintaining immunostimulatory activity in the presence of host RNases.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If lactic acid bacteria are treated with cell wall-digesting enzymes, then the IL-12 production-inducing ability is spoiled, but using enzyme-resistant strains maintains the ability

Engineering Contradiction:
ImproveIL-12 production-inducing abilityVSAvoidresistance to enzymatic treatment
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent transforms the harmful effect of cell wall-digesting enzymes into a beneficial selection mechanism. By identifying bacteria that naturally resist these enzymes, the invention converts what would normally be a destructive force into a tool for selecting and isolating superior strains with enhanced stability and immunostimulatory properties.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent employs disposable test substrates and model systems to screen and identify enzyme-resistant bacterial strains. Rather than developing complex protective mechanisms, the invention uses simple, expendable test materials to rapidly identify and select bacteria that inherently possess the desired resistance properties, making the discovery process efficient and cost-effective.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Reliability

If RNases are present in the environment and products, then they contaminate products and remain after sterilization, but using RNase-resistant bacteria maintains RNA integrity

Engineering Contradiction:
ImproveRNA integrityVSAvoidRNase contamination
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent converts the ubiquitous presence of RNases in the environment into a beneficial feature by selecting bacteria that produce RNase-resistant RNA. The harmful RNase contamination becomes a selective pressure that identifies and promotes bacteria with superior RNA protection mechanisms, turning an environmental hazard into a quality assurance tool.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The bacteria themselves provide the solution to their own vulnerability by producing RNA molecules with inherent resistance to RNase degradation. This self-service mechanism eliminates the need for external protective measures, as the bacteria's own genetic machinery produces the protective RNA structures that safeguard their immunostimulatory function against environmental RNases.

Inventive Principle:
Principle #25Self-service

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 MCC1849 strain effectively promotes IL-12 production and enhances cell-mediated immunity, offering robust prophylactic and therapeutic benefits against infections, including influenza, with minimal reduction in activity due to enzymatic treatments.

Implementation Method 1

lactic acid bacteria belonging to Lactobacillus casei induce production of cytokines such as IL-12 (interleukin-12) and IFN-γ (interferon-γ) by immunocompetent cells of hosts to activate cell-mediated host immunity

Methodology Applied
Scientific EffectCytokine induction:

Implementation Method 2

lactic acid bacteria are treated with a cell wall-digesting enzyme (N-acetyl muramidase), the IL-12 production-inducing ability is spoiled

Methodology Applied
Scientific EffectEnzymatic degradation: Enzyme

Implementation Method 3

dead cells of lactic acid bacteria killed by heating are treated with RNase, the IL-12 production-inducing ability is markedly spoiled

Methodology Applied
Scientific EffectRNase degradation: Enzyme

Data Source

PatentUS11241463B2Lactic acid bacterium, drug, food or drink, and feed which contain the lactic acid bacterium
Publication Date: 2022.02.08 MORINAGA MILK IND CO LTD
  • US11241463B2 patent drawing
  • US11241463B2 patent drawing

AI summary

A composition includes cells of Lactobacillus paracasei MCC1849 (NITE BP-01633). The composition is in the form of a pharmaceutical composition, a food, a drink, or a feed. The pharmaceutical composition can be used for treating an inflammatory disease, ulcer, food allergies, bronchial asthma, urticaria, pollinosis, anaphylactic shock or an opportunistic infection.