TABLE 2.
Examples of LBTs for disease diagnosis and/or treatment.
| Condition | Biomarker | Genetic sensor/inducer system(s) | Actuator(s)/other synthetic feature(s) | Chassis | Model systems | Ref |
|---|---|---|---|---|---|---|
| IBD | Thiosulfate | ThsSR-P phsA TCS-cognate promoter pair for thiosulfate detection and signal relay | sfGFP, hly-avCys (signal peptide-linked AvCystatin) reporter, therapeutic payload modules BE2-sgRNA based editor module | EcN | Mouse | Zou et al. (2023) |
| Thiosulfate, tetrathionate | ThsSR-P phsA and TtrSR-P ttrB to sense thiosulfate and tetrathionate, respectively | sfGFP reporter | EcN | Mouse | Daeffler et al. (2017) | |
| Nitrate, thiosulfate | NarXL-PyeaR to sense nitrate. Boolean AND logic gate by using additional ThsSR-P phsA and the nitrate sensor module | sfGFP reporter ΔnarXL (deletion of native NarXL) | EcN | Mouse | Woo et al. (2020) | |
| Tetrathionate | Tetrathionate sensor TtrSR with cognate promoters P ttrSR and P ttrBCA | Cro-inducible CI/Cro bistable switch-based cell memory record | E. coli | Mouse | Riglar et al. (2017) | |
| NGF-1 | ||||||
| Nitric oxide | Enhancer binding protein NorR and the cognate promoter P norV | DNA recombinase fimE to control bidirectional CFP (cyan fluorescence protein), YFP (yellow fluorescence protein) reporter switch | E. coli TOP10 | Mouse ileum explant culture | Archer et al. (2012) | |
| Calprotectin | Zinc-responsive native promoter of ykgMO | sfGFP reporter | EcN | Mouse | Xia et al. (2023) | |
| Dietary xylan | B. ovatus xylanase promoter (xylanase operon) | murine interleukin-2 (MuIL2) | B. ovatus | In vitro culture | Farrar et al. (2005) | |
| B. ovatus xylanase promoter (GenBank EU334491) | Human keratinocyte growth factor-2 (hKGF-2) | B. ovatus | Mouse | Hamady et al. (2010) | ||
| Identical to Hamady et al. (2010) | Human transforming growth factor-β (hTGF-β) | B. ovatus | Mouse | Hamady et al. (2011) | ||
| CDI | Sialic acid | Sialic acid sensor NanR-P NanA and a transcriptional activator CadC-P CadBA (signal amplifier) | Cbh (Choloyglycine hydrolase) under the control of P CadBA | EcN | Mouse | Koh et al. (2022) |
| V. cholerae | Cholerae autoinducer-1 (CAI-1) | A chimeric sensor composed of the membrane binding domain of CqsS (the CAI-1 receptor) and the signal transduction domain of NisK (the signal transduction domain of NisRK TCS), with cognate P nisA | TetR-inducible transcriptional inverter circuit containing either mCherry or β-lactamase gene | Lactococcus lactis | Mouse | Mao et al. (2018) |
| A phosphorelay system of CqsS, LuxU and LuxO that controls the activity of tpqrr4 promoter | guide RNA (gRNA) for the repression of ‘lysis and kill’ pBAD-YebF-Art-085 cassette, upon binding with constitutively expressed dCas9 | E. coli MG1655 | In vitro culture | Jayaraman et al. (2017) | ||
| P. aeruginosa | N-acyl homoserine lactone (AHL) | P tetR based expression of AHL-sensing transcription factor LasR, which activates its cognate promoter P luxR | Pyocin S5, and Lysis E7 | E. coli TOP10 | Co-culture in vitro | Saeidi et al. (2011) |
| The ‘sense-kill’ genetic system identical to Saeidi et al. (2011) | Pyocin S5, Lysis E7, and Dispersin B. D-ala auxotrophic genotype Δalr ΔdadX for plasmid maintenance | EcN | C. elegans, mouse | Hwang et al. (2017) | ||
| Methicillin-resistant Staphylococcus aureus (MRSA) | Autoinducer peptide-I (AIP-I) | AIP-I sensing TCS AgrCA and the cognate P3 promoter | GusA reporter | Lactobacillus reuteri | In vitro culture | Lubkowicz et al. (2018) |
| Enterococcal infection | Enterococcal sex pheromone cCF10 | cCF10-responsive regulator PrgX that activates promoter PQ upon cCF10 binding | Anti-enterococcal peptides EntA, EntP, HirJM79 | L. lactis | In vitro culture | Borrero et al. (2015) |
| Citrobacter rodentium | Fucose | Promoter region upstream of E. coli fucPIK genes | GFP reporter | E. coli BW25113 | Mouse | Pickard et al. (2014) |
| Gastrointestinal health | Heme, AHL, thiosulfate | Heme-responsive transcriptional repressor HrtR and the cognate synthetic promoter P L(HrtO) , or AHL-sensor LasR- P luxR , or thiosulfate sensor ThsSR-P phsA | LuxCDABE luciferase and a wireless luminometer that relays luminescence into electric readouts (ingestible micro-bio-electronic device; IMBED). ChuA for extracellular heme transit | EcN | Mouse, swine | Mimee et al. (2018) |
| Liver metastasis | IPTG | IPTG-inducible expression system LacI-P tac | LacZ reporter | EcN | Mouse | Danino et al. (2015) |
| Tumor | Tumor-specific agent(s) | Tumor-responsive regulatory elements in Salmonella Typhimurium genome screened using the promoter-trap library | GFP_ovalbumin low-stability reporter | Attenuated Salmonella enterica subsp. enterica serovar Typhimurium | Mouse, colon carcinoma cells | Leschner et al. (2012) |
| IPTG | IPTG-inducible expression system LacI-P tac | Episomally-maintained IPTG-inducible KfiC in ΔkfiC genomic background | EcN | Mouse | Harimoto et al. (2022) | |
| Anoxic condition | Anaerobic-inducible FNR-P fnrS | DacA (STING-agonist cyclic di-AMP), ΔthyA, ΔdapA | EcN | Mouse, human antigent-presenting cells | Leventhal et al. (2020) | |
| Lactic acid, anoxic condition, pH | Lactic-acid inducible LldR-P LldR , anaerobic-inducible FNR-P fnrS , pH-sensitive CadC-P CadC expression systems | GFP reporter, Δasd, Δglms | EcN | Tumor condition-mimicking spheroid coculture system, mouse | Chien et al. (2022) | |
| Lactate-hypoxia Boolean AND logic gate to enhance tumor-specific localization | ||||||
| AHL | A synchronized lysis circuit using coupled positive and negative feedback loops, using P luxl that controls LuxI expression | Positive feedback: LuxI under the control of P luxl produces AHL, which binds constitutively produced LuxR to drive P luxl expression | Attenuated S. Typhimurium | Mouse | Din et al. (2016) | |
| Inflammation, diabetes | Nitrogen oxides, glucose | Nitrate/nitrite-sensitive transcriptional promoter P YeaR , glucose sensitive promoter P CpxP | Negative feedback: cell death triggered by bacteriophage lysis gene (φX174 E). sfGFP reporter and HlyE (hemolysin) | BxB1 and TP901 integrase (genetic switches)-mediated Boolean logic gates, GFP and RFP as actuators | E. coli DH5αZ1 Urine, serum samples | Courbet et al. (2015) |
| Bacillus subtilis Hyperammonemia | Anoxic condition | Anaerobic-inducible FNR-P fnrS | ArgAfbr., ΔthyA, ΔargR | EcN | Mouse | Kurtz et al. (2019) |
| Enteric hyperoxaluria | Anoxic condition | Anaerobic-inducible FNR-P fnrS | OxlT, OxdC, Frc, ScAAE3, ΔthyA | EcN | Mouse | Lubkowicz et al. (2022) |
| Homocystinuria | IPTG | IPTG-inducible expression system LacI-P tac | MetD, MetC, MetP, ΔyjeH | EcN | Human clinical trial (NCT05462132) | Perreault et al. (2021) |
| PKU | IPTG, L-arabinose, anoxic condition | IPTG-inducible LacI-P tac , L-arabinose inducible AraC-P BAD , anaerobic-inducible FNR-P fnrS | PAL (5 copies), PheP (2 copies), LAAD, ΔdapA | EcN | Human clinical trial (NCT04534842) | Isabella et al. (2018) |
| Identical to Isabella et al. (2018) | Identical to Isabella et al. (2018) except for a mutant PAL (mPAL) | EcN | Human clinical trial (NCT05764239) | Adolfsen et al. (2021) | ||
| PhlF-P PhlF repressor, IPTG-inducible LacI-P tac , AraC-P BAD | mPAL (3 copies) and PheP (1 copy) under P PhlF control. LAAD under P BAD control, ΔdapA | EcN | In vitro culture | Triassi et al. (2023) |