Engineered Probiotics with Dual Promoters for Pathogen Control
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Solution Overview
Problem
The increasing emergence of antibiotic-resistant foodborne pathogens, such as Salmonella, poses a significant threat due to the widespread use of antibiotics in agriculture, leading to the need for alternative antimicrobial solutions to reduce pathogen loads in animals and prevent human disease.
Innovation Solution
Engineered antimicrobial probiotics with genetically modified bacteria expressing antimicrobial peptides under specific promoters responsive to gastrointestinal tract conditions, allowing for targeted and tunable expression and secretion of antimicrobial proteins to effectively control pathogens.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antibiotics are used to control foodborne pathogens in agriculture, then pathogen loads are reduced, but antibiotic resistance emerges and spreads
Solution Approach 1:
The patent changes the fundamental parameter of antimicrobial mechanism by replacing traditional antibiotics with engineered probiotics that produce antimicrobial peptides through controlled gene expression. The probiotics express antimicrobial proteins under specific promoters responsive to gastrointestinal conditions, fundamentally altering how pathogen control is achieved without using conventional antibiotics, thereby preventing resistance development.
Solution Approach 2:
The engineered probiotic bacteria serve as an intermediary organism that delivers antimicrobial peptides directly to the gastrointestinal tract where pathogens reside. Rather than administering antibiotics systemically, the probiotics colonize the gut and locally produce antimicrobial compounds, creating a targeted delivery system that reduces off-target effects and resistance selection pressure.
2Productivity
If antibiotics are used to promote growth and improve feed efficiency in livestock, then productivity increases, but resistance reservoirs are created
Solution Approach 1:
The patent extracts the growth-promoting function from antibiotic therapy by using engineered probiotics that produce antimicrobial peptides specifically targeted at pathogens while leaving beneficial gut microbiota unaffected. This selective approach removes the harmful side effect of disrupting the microbiome and selecting for resistance, while maintaining the productivity benefit through improved gut health and pathogen control.
Solution Approach 2:
The probiotics provide localized antimicrobial action within the gastrointestinal tract through spatially and temporally controlled expression of antimicrobial peptides. The promoters are designed to respond to specific gastrointestinal conditions, ensuring that antimicrobial production occurs only where needed (in the gut) and under appropriate conditions, rather than systemically throughout the organism.
3Device complexity
If single-promoter probiotic systems are used to deliver antimicrobial peptides, then genetic construct simplicity is maintained, but effectiveness varies across different gastrointestinal microenvironments
Solution Approach 1:
The patent segments the gastrointestinal tract into different microenvironmental zones and assigns different promoter types to target specific zones. By using multiple promoters with distinct induction characteristics (e.g., nutrient-responsive, pH-responsive, oxygen-responsive), the system divides the challenge of covering all gut environments into manageable segments, each handled by a specialized promoter-probiotic combination.
Solution Approach 2:
The patent introduces dynamic gene expression control through promoters that respond to changing gastrointestinal conditions. Rather than using static constitutive promoters, the system employs dynamic promoters that are induced by specific environmental signals (nutrient availability, pH, redox state), allowing the probiotics to adapt their antimicrobial peptide production to the prevailing microenvironmental conditions in real-time.
Data Source
AI summary
Embodiments herein relate to engineered antimicrobial probiotics for the treatment of gastrointestinal tract pathogens. In an embodiment, a composition for treatment of an animal is included. The composition can include a first genetically engineered bacterium comprising a first exogenous polynucleotide. The first exogenous polynucleotide can include a first heterologous promoter and a first polynucleotide that encodes a first antimicrobial protein. The composition can also include a second genetically engineered bacterium comprising a second exogenous polynucleotide. The second exogenous polynucleotide can include a second heterologous promoter and a second polynucleotide that encodes a second antimicrobial protein. The first heterologous promoter can be induced by one set of exogenous environmental conditions found in the gastrointestinal tract of the animal and the second heterologous promoter can be induced by a second set of exogenous environmental conditions found in the gastrointestinal tract of the animal. Other embodiments are also included herein.