Engineered Microbe Detecting Pseudomonas aeruginosa via Quorum Sensing
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Solution Overview
Problem
Current strategies for combating Pseudomonas aeruginosa infections, such as antibiotic chemotherapy and bacteriophage therapy, are limited by antibiotic resistance and unspecific killing, which can disrupt the healthy human microbiome and have limited therapeutic potential due to host antibody responses.
Innovation Solution
Development of an engineered microbial system using synthetic biology that includes a nucleic acid molecule with a protein for detecting Pseudomonas aeruginosa and an antimicrobial peptide, where the peptide production is induced by a promoter activated by the pathogen, allowing for targeted killing of the bacteria.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antibiotic chemotherapy is used to treat Pseudomonas aeruginosa infections, then bacterial killing is achieved, but antibiotic resistance develops and the healthy human microbiome is disrupted
Solution Approach 1:
The patent employs strain-specific bacteriocins that are selectively effective against P. aeruginosa while sparing other bacteria in the microbiome. The system uses a promoter induced by P. aeruginosa quorum sensing molecules to locally produce the antimicrobial peptide only where and when needed, achieving targeted killing without broad-spectrum antibiotic effects.
Solution Approach 2:
The engineered microbe uses the pathogen's own quorum sensing system to trigger its antimicrobial response. The promoter is activated by P. aeruginosa signals, allowing the host microbe to sense and respond to the pathogen's presence, effectively using the pathogen's own mechanisms against it.
2Reliability
If bacteriophage therapy is used to treat Pseudomonas aeruginosa infections, then pathogen-specific killing is achieved, but therapeutic potential is limited by host antibody responses
Solution Approach 1:
The patent uses a disposable, non-replicating antimicrobial peptide system that does not require viral replication or host cell entry. The peptide is produced by the engineered microbe and directly kills the pathogen without triggering viral antibody responses, offering a simpler, more versatile therapeutic approach that can be administered repeatedly.
3Reliability
If combinatorial antibiotic treatment is used to address rapid drug tolerance, then bacterial killing is improved, but unspecific killing increases and microbiome health deteriorates
Solution Approach 1:
The system produces strain-specific bacteriocins that are selectively effective against P. aeruginosa. The promoter is specifically induced by P. aeruginosa quorum sensing molecules, ensuring that the antimicrobial peptide is only produced in response to the pathogen's presence, thereby achieving targeted killing without affecting commensal bacteria.
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 engineered system effectively senses and eradicates Pseudomonas aeruginosa, providing a novel antimicrobial strategy that avoids reliance on traditional antibiotics and minimizes disruption to the human microbiome, with demonstrated bactericidal activity and biofilm inhibition.
Implementation Method 1
a first nucleotide sequence encoding a protein that detects the presence, amount or both of a pathogenic microorganism by forming a complex with a protein produced by said pathogenic microorganism
Implementation Method 2
the second nucleotide sequence is under control of a promoter that is induced by the complex of the protein encoded by the first nucleotide sequence and the protein produced by said pathogenic microorganism
Implementation Method 3
a second nucleotide sequence encoding an antimicrobial peptide, wherein the antimicrobial peptide is effective against the pathogenic microorganism detected by the protein encoded by the first nucleotide sequence
Data Source
AI summary
The present invention relates to an isolated nucleic acid molecule comprising a first nucleotide sequence encoding a protein that detects the presence, amount or both of a pathogenic microorganism by forming a complex with a protein produced by said pathogenic microorganism; a second nucleotide sequence encoding an antimicrobial peptide, wherein the antimicrobial peptide is effective against the pathogenic microorganism detected by the protein encoded by the first nucleotide sequence, wherein the second nucleotide sequence is under control of a promoter that is induced by the complex of the protein encoded by the first nucleotide sequence and the protein produced by said pathogenic microorganism. A recombinant microorganism comprising the isolated nucleic acid molecule and a method of sensing and killing pathogenic microorganisms is also described.