Engineered Microbe Quorum Sensing Pathogen Detection
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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, highlighting the need for novel antimicrobial approaches.
Innovation Solution
An engineered microbe equipped with a nucleic acid molecule that detects Pseudomonas aeruginosa through quorum sensing molecules, inducing the production of antimicrobial peptides or antibiofilm enzymes, and optionally controlling host motility to target the pathogen, using a synthetic biology framework.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antibiotic chemotherapy is used to treat Pseudomonas aeruginosa infections, then the pathogen is killed, but the healthy human microbiome is disrupted and antibiotic resistance develops
Solution Approach 1:
The engineered microbe produces antimicrobial peptides specifically targeted at Pseudomonas aeruginosa through quorum sensing activation, creating localized antimicrobial activity only where the pathogen is detected, thereby avoiding broad-spectrum effects on the healthy microbiome while maintaining high effectiveness against the pathogen
Solution Approach 2:
The engineered microbe autonomously detects Pseudomonas aeruginosa through quorum sensing molecules and activates antimicrobial peptide production in response, enabling self-regulated targeted killing without requiring external antibiotic administration, thus avoiding microbiome disruption and resistance development
2Reliability
If bacteriophage therapy is used to treat Pseudomonas aeruginosa infections, then the pathogen is destroyed, but the treatment cannot be re-employed after host develops antibodies
Solution Approach 1:
The engineered microbe constitutively expresses antimicrobial peptides that remain active and reusable throughout the treatment period, allowing repeated application without host antibody development issues, as the antimicrobial mechanism is cellular and metabolic rather than viral
Solution Approach 2:
The engineered microbe serves multiple functions: it detects Pseudomonas aeruginosa through quorum sensing, produces antimicrobial peptides for killing, and can be administered repeatedly without losing efficacy, providing a versatile and reusable treatment approach
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 microbe effectively senses and kills Pseudomonas aeruginosa, inhibiting its growth and biofilm formation while minimizing harm to the human microbiome, offering a targeted and specific antimicrobial strategy.
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 quorum sensing molecule produced by said pathogenic microorganism
Implementation Method 2
one or more second nucleotide sequence said one or more second nucleotide sequence being under control of a promoter that is induced by the complex of the protein encoded by the first nucleotide sequence and the quorum sensing molecule produced by said pathogenic microorganism and encoding (i) an antimicrobial peptide, wherein the antimicrobial peptide is effective against the pathogenic microorganism detected by the protein encoded by the first nucleotide sequence
Implementation Method 3
an antibiofilm enzyme, wherein the antibiofilm enzyme 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) a first nucleotide sequence encoding a protein that detects the presence, amount or both of a pathogenic microorganism by forming a complex with a quorum sensing molecule produced by said pathogenic microorganism, (b) one or more second nucleotide sequence said one or more second nucleotide sequence being under control of a promoter that is induced by the complex of the protein encoded by the first nucleotide sequence and the quorum sensing molecule produced by said pathogenic microorganism and encoding (i) an antimicrobial peptide, wherein the antimicrobial peptide is effective against the pathogenic microorganism detected by the protein encoded by the first nucleotide sequence; and/or an antibiofilm enzyme wherein the antibiofilm enzyme is effective against the pathogenic microorganism detected by the protein encoded by the first nucleotide sequence; and (c) optionally a third nucleotide sequence encoding a protein that controls the motility of the host organism, wherein the protein that controls the motility of the host organism directs the motility of the host organism towards said pathogenic microorganism. A recombinant microorganism comprising the isolated nucleic acid molecule and a method of sensing and killing pathogenic microorganisms is also described.