Genetically Modified Lactic Acid Bacteria for Antimicrobial Peptide Delivery
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Solution Overview
Problem
Current methods for producing and delivering antimicrobial peptides (AMPs) are costly, time-consuming, and face challenges such as rapid degradation and immune system clearance, limiting their therapeutic effectiveness against antibiotic-resistant bacteria like Enterococci.
Innovation Solution
Genetically modified microbes, specifically lactic acid bacteria, are engineered to express and secrete antimicrobial peptides in response to specific triggers, allowing targeted delivery and enhanced bioavailability within the gastrointestinal tract to combat antibiotic-resistant Enterococci.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional antibiotic molecules are used, then broad antimicrobial activity is achieved, but antibiotic resistance develops among pathogenic bacteria
Solution Approach 1:
The patent transitions from using traditional antibiotic molecules to antimicrobial peptides, representing a fundamental parameter change in the chemical structure and mechanism of action. This change enables broad-spectrum antimicrobial activity while avoiding the resistance issues associated with conventional antibiotics, as the peptides act through physical disruption of bacterial membranes rather than through specific molecular targets that bacteria can mutate to resist.
Solution Approach 2:
The invention employs a dual-component system consisting of a probiotic microbe and an antimicrobial peptide. The probiotic serves as a delivery vehicle that colonizes the gastrointestinal tract and provides a safe habitat, while the antimicrobial peptide acts as the active antimicrobial agent. This composite approach allows the therapeutic to persist in the body and continuously combat resistant bacteria without the harmful side effects of traditional antibiotics.
2Reliability
If antimicrobial peptides are administered systemically, then broad coverage is achieved, but rapid clearance by the immune system occurs
Solution Approach 1:
The patent introduces a probiotic microbe as an intermediary carrier to deliver the antimicrobial peptide to the target site. Instead of administering the peptide systemically where it would be rapidly cleared by the immune system, the probiotic serves as a protected vehicle that transports the peptide through the gastrointestinal tract and into the body, releasing it at the appropriate location and time. This intermediary approach extends the duration of action and ensures sustained antimicrobial coverage.
Solution Approach 2:
The probiotic microbe is selected from the patient's own gastrointestinal flora, making the system self-service in nature. The probiotic naturally colonizes the gastrointestinal tract and provides a safe habitat, continuously producing and secreting the antimicrobial peptide locally. This self-sustaining system eliminates the need for repeated systemic administrations and maintains prolonged antimicrobial activity without triggering immune clearance.
3Reliability
If high concentrations of antimicrobial peptides are used, then therapeutic effectiveness is improved, but toxic side effects increase
Solution Approach 1:
The patent implements local production and secretion of antimicrobial peptides by probiotic microbes colonizing the gastrointestinal tract. Rather than distributing high concentrations of peptides systemically which would cause toxic side effects, the system produces the peptides locally at the site where they are needed. This localized approach ensures high therapeutic effectiveness against pathogenic bacteria in the gastrointestinal tract while avoiding the toxic effects associated with high systemic concentrations.
4Quantity of substance
If solid state peptide synthesis is used, then antimicrobial peptides are produced, but production cost and time increase
Solution Approach 1:
The patent employs probiotic microbes as living factories that self-produce and secrete antimicrobial peptides through their natural metabolic processes. Instead of using expensive and time-consuming solid state peptide synthesis methods, the probiotic organisms autonomously synthesize the peptides and release them into the surrounding environment. This self-service production system dramatically reduces manufacturing costs and time while enabling continuous production of the therapeutic peptides.
Data Source
AI summary
Provided herein are genetically modified microbes. In one embodiment, a genetically modified microbe includes an exogenous polynucleotide that includes a pheromone-responsive region. In one embodiment, the pheromone-responsive region is derived from a conjugative plasmid from a member of the genus Enterococcus spp. The pheromone-responsive region includes a pheromone-responsive promoter and an operably linked coding region encoding an antimicrobial peptide. In one embodiment, a genetically modified microbe includes an exogenous polynucleotide that includes a promoter and an operably linked coding sequence encoding an antimicrobial peptide, where expression of the coding region is controlled by a modulator polypeptide and is altered by a modulating agent, and where the coding region encodes an antimicrobial peptide.