Bacterial contamination sensor (AI-2 + CRISPRi)

Flags general bacterial contamination by sensing autoinducer-2 (AI-2), the inter-species quorum signal made by most bacteria. The LsrR/AI-2 system gates a CRISPRi circuit driving a visible pigment, in safe E. coli K-12.

Pathogen signalBSL-1 chassistemplateAI-2quorum-sensingcontaminationpathogenwaterfood-safetyCRISPRi
Input
Autoinducer-2 (AI-2 / DPD)
Pathogen signal
Sense
CRISPRi-repression
dCas9 (S. pyogenes, catalytically dead)
Chassis
E. coli K-12 (MG1655)
BSL-1
Output
amilCP
pigment

What it detects

Analyte
Autoinducer-2 (AI-2 / DPD) — LsrR/AI-2 system responds from sub-µM AI-2
Category
Pathogen signal
Signal
AI-2, the universal inter-species quorum signal secreted by a broad range of bacteria — a proxy for general microbial contamination

Genetic circuit

⤢ click to enlarge

Genetic construct (SBOL)

The DNA construct as transcription units, drawn with SBOL Visual part glyphs.

⤢ click to enlarge

CRISPR sensing mechanism

Strategy
CRISPRi-repression · NOT logic
Cas protein
dCas9 (S. pyogenes, catalytically dead)
Analyte sensor
Imported AI-2 is phosphorylated and binds the LsrR repressor, de-repressing the lsr (Plsr) promoter.
Signal flow
AI-2 -> phospho-AI-2 releases LsrR -> Plsr transcribes an anti-pigment sgRNA -> dCas9 + sgRNA repress a constitutive amilCP cassette (CRISPRi) -> pigment fades when bacteria are present (NOT gate); add an inverter for colour-on.

Safe chassis

E. coli K-12 (MG1655)Escherichia coli

The non-pathogenic laboratory workhorse. K-12 strains have lost the ability to colonize the human gut and are the reference BSL-1 host for genetic engineering, with the deepest tooling of any bacterial chassis.

BSL-1

Genetic parts

PartRoleSource / id
LsrR repressor + Lsr transport
AI-2-responsive repressor; native to E. coli.
regulatorE. coli lsr operon
Plsr promoter
De-repressed by phospho-AI-2.
promoterE. coli lsr operon promoter
Anti-pigment sgRNAsgRNAdesigned against the amilCP promoter
sgRNA scaffold (SpCas9)
GTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGC
sgRNAStandard SpCas9 scaffold
dCas9dCas9Qi et al. 2013, Cell (CRISPRi)
amilCP chromoprotein
Naked-eye pigment.
reporterBBa_K592009

Output & readout

Type
pigment
Reporter
amilCP
Readout
Visible pigment (naked eye / smartphone)
Positive result
Colour change indicates bacterial quorum signal in the sample.

Performance

Limit of detection
LsrR/AI-2 module: sub-µM AI-2 (module-validated).
Dynamic range
~0.1-10 µM AI-2
Response time
~240 min
Device validated
No — design template (parts validated individually)

Detects a broad bacterial signal rather than one species; the LsrR AI-2 system and CRISPRi are validated separately and the integrated device is a design template.

Safety

Biosafety level
BSL-1 (non-pathogenic chassis)
GRAS chassis
No
Biocontainment
Safe E. coli K-12 reads a secreted small molecule; no pathogen handled.
Field-deployable
Lab / supervised use

Indirect, safe detection of contamination via a quorum signal.

Build & run

#StageStep
1designDesign anti-pigment sgRNA
Target the amilCP promoter; check host off-targets.
2assemblyAssemble units
TU1: Plsr -> sgRNA (native Lsr import/LsrR). TU2: dCas9 + constitutive amilCP.
3transformationTransform E. coli K-12
Select; confirm baseline pigment without AI-2.
4inductionAdd sample
Incubate with the water/food sample + AI-2 (DPD) standard curve.
5readoutScore colour
Compare pigment to the curve.

Source & parts

Design
Design template combining the LsrR/AI-2 quorum-sensing module with E. coli CRISPRi
Parts validated in
  • Xavier & Bassler 2005 / E. coli lsr-AI-2 system
  • Qi et al. 2013, Cell (CRISPRi)
License
Parts per their original sources; design template CC BY 4.0