Engineered bacteria as living therapeutics: Next-generation precision tools for health, industry, environment, and agriculture

Imen Zalila-Kolsi; Imen Zalila-Kolsi

doi:10.3934/microbiol.2025042

AIMS Microbiology

2025, Volume 11, Issue 4: 946-962. doi: 10.3934/microbiol.2025042

Previous Article Next Article

Review

Engineered bacteria as living therapeutics: Next-generation precision tools for health, industry, environment, and agriculture

Imen Zalila-Kolsi ^,

College of Medical and Health Sciences, Liwa University, Abu Dhabi P.O. Box 41009, United Arab Emirates

Received: 03 October 2025 Revised: 04 December 2025 Accepted: 10 December 2025 Published: 15 December 2025

Synthetic biology has revolutionized precision medicine by enabling the development of engineered bacteria as living therapeutics, dynamic biological systems capable of sensing, responding to, and functioning within complex physiological environments. These microbial platforms offer unprecedented adaptability, allowing for real-time detection of disease signals and targeted therapeutic delivery. This review explores recent innovations in microbial engineering across medical, industrial, environmental, and agricultural domains. Key advances include CRISPR-Cas systems, synthetic gene circuits, and modular plasmid architectures that provide fine-tuned control over microbial behavior and therapeutic output. The integration of computational modeling and machine learning has further accelerated design, optimization, and scalability. Despite these breakthroughs, challenges persist in maintaining genetic stability, ensuring biosafety, and achieving reproducibility in clinical and industrial settings. Ethical and regulatory frameworks are evolving to address dual-use concerns, public perception, and global policy disparities. Looking forward, the convergence of synthetic biology with nanotechnology, materials science, and personalized medicine is paving the way for intelligent, responsive, and sustainable solutions to global health and environmental challenges. Engineered bacteria are poised to become transformative tools not only in disease treatment but also in diagnostics, biomanufacturing, pollution mitigation, and sustainable agriculture.
- Engineered bacteria,
- living therapeutics,
- synthetic biology,
- CRISPR-Cas systems,
- microbiome engineering
Citation: Imen Zalila-Kolsi. Engineered bacteria as living therapeutics: Next-generation precision tools for health, industry, environment, and agriculture[J]. AIMS Microbiology, 2025, 11(4): 946-962. doi: 10.3934/microbiol.2025042

Related Papers:

Abstract

Synthetic biology has revolutionized precision medicine by enabling the development of engineered bacteria as living therapeutics, dynamic biological systems capable of sensing, responding to, and functioning within complex physiological environments. These microbial platforms offer unprecedented adaptability, allowing for real-time detection of disease signals and targeted therapeutic delivery. This review explores recent innovations in microbial engineering across medical, industrial, environmental, and agricultural domains. Key advances include CRISPR-Cas systems, synthetic gene circuits, and modular plasmid architectures that provide fine-tuned control over microbial behavior and therapeutic output. The integration of computational modeling and machine learning has further accelerated design, optimization, and scalability. Despite these breakthroughs, challenges persist in maintaining genetic stability, ensuring biosafety, and achieving reproducibility in clinical and industrial settings. Ethical and regulatory frameworks are evolving to address dual-use concerns, public perception, and global policy disparities. Looking forward, the convergence of synthetic biology with nanotechnology, materials science, and personalized medicine is paving the way for intelligent, responsive, and sustainable solutions to global health and environmental challenges. Engineered bacteria are poised to become transformative tools not only in disease treatment but also in diagnostics, biomanufacturing, pollution mitigation, and sustainable agriculture.

Conflict of interest

The authors declare no conflict of interest.

Author contributions

The author confirms sole responsibility for the conception, literature review, analysis, writing, and final approval of the manuscript.

References

[1]	Yan Q, Ming Y, Liu J, et al. (2025) Microbial biotechnology: from synthetic biology to synthetic ecology. Adv Biotechnol 3: 1, s44307-024-00054-4. https://doi.org/10.1007/s44307-024-00054-4
[2]	Kim K, Kang M, Cho BK (2023) Systems and synthetic biology-driven engineering of live bacterial therapeutics. Front Bioeng Biotechnol 11: 1267378. https://doi.org/10.3389/fbioe.2023.1267378
[3]	Zhen W, Wang Z, Wang Q, et al. (2024) Cardiovascular disease therapeutics via engineered oral microbiota: Applications and perspective. iMeta 3: e197. https://doi.org/10.1002/imt2.197
[4]	Chang X, Liu X, Wang X, et al. (2025) Resynthesis of synthetic biology techniques: combining engineered bacteria with other antitumour therapies. Front Microbiol 16: 1545334. https://doi.org/10.3389/fmicb.2025.1545334
[5]	Woo SG, Kim SK, Lee SG, et al. (2025) Engineering probiotic Escherichia coli for inflammation-responsive indoleacetic acid production using RiboJ-enhanced genetic circuits. J Biol Eng 19: 10. https://doi.org/10.1186/s13036-025-00479-y
[6]	Chang Z, Guo X, Li X, et al. (2025) Bacterial immunotherapy leveraging IL-10R hysteresis for both phagocytosis evasion and tumor immunity revitalization. Cell 188: 1842-1857.e20. https://doi.org/10.1016/j.cell.2025.02.002
[7]	Pitzalis MF, Sadler JC (2025) Chemical bio-manufacture from diverse C-rich waste polymeric feedstocks using engineered microorganisms. RSC Sustainability 3: 1672-1684. https://doi.org/10.1039/D5SU00013K
[8]	Gutierrez MM, Reed JA, McElroy RA, et al. (2024) Bacteria encapsulation into polyethylene glycol hydrogels using Michael-type addition reactions. MRS Adv 9: 1520-1526. https://doi.org/10.1557/s43580-024-00940-y
[9]	Zhang S, Elbs-Glatz Y, Tao S, et al. (2025) Probiotics promote cellular wound healing responses by modulating the PI3K and TGF-β/Smad signaling pathways. Cell Commun Signal 23: 195. https://doi.org/10.1186/s12964-025-02179-y
[10]	Jinek M, Chylinski K, Fonfara I, et al. (2012) A programmable Dual-RNA–Guided DNA endonuclease in adaptive bacterial immunity. Science 337: 816-821. https://doi.org/10.1126/science.1225829
[11]	Hidalgo-Cantabrana C, Goh YJ, Barrangou R (2019) Characterization and repurposing of type i and type ii crispr–cas systems in bacteria. J Mol Biol 431: 21-33. https://doi.org/10.1016/j.jmb.2018.09.013
[12]	Liu Z, Schiel JA, Maksimova E, et al. (2020) ErCas12a CRISPR-MAD7 for model generation in human cells, Mice, and Rats. The CRISPR J 3: 97-108. https://doi.org/10.1089/crispr.2019.0068
[13]	Rong Y, Frey A, Özdemir E, et al. (2024) CRISPRi-mediated metabolic switch enables concurrent aerobic and synthetic anaerobic fermentations in engineered consortium. Nat Commun 15: 8985. https://doi.org/10.1038/s41467-024-53381-4
[14]	Wu J, Ye W, Yu J, et al. (2025) Engineered bacteria and bacterial derivatives as advanced therapeutics for inflammatory bowel disease. Essays Biochem 69: 169-179. https://doi.org/10.1042/EBC20253003
[15]	Nguyen DH, You SH, Ngo HTT, et al. (2024) Reprogramming the tumor immune microenvironment using engineered dual-drug loaded Salmonella. Nat Commun 15: 6680. https://doi.org/10.1038/s41467-024-50950-5
[16]	Zhang H, Ma J, Wu Z, et al. (2024) BacPE: a versatile prime-editing platform in bacteria by inhibiting DNA exonucleases. Nat Commun 15: 825. https://doi.org/10.1038/s41467-024-45114-4
[17]	Taschner M, Dickinson JB, Roisné-Hamelin F, et al. (2024) 4G cloning: rapid gene assembly for expression of multisubunit protein complexes in diverse hosts. Life Sci Alliance 8: e202402899. https://doi.org/10.26508/lsa.202402899
[18]	Flynn RA, Pedram K, Malaker SA, et al. (2021) Small RNAs are modified with N-glycans and displayed on the surface of living cells. Cell 184: 3109-3124.e22. https://doi.org/10.1016/j.cell.2021.04.023
[19]	Hsieh YE, Tandon K, Verbruggen H, et al. (2024) Comparative analysis of metabolic models of microbial communities reconstructed from automated tools and consensus approaches. npj Syst Biol Appl 10: 54. https://doi.org/10.1038/s41540-024-00384-y
[20]	Jin L, Yu S, Cheng J, et al. (2025) Machine learning powered inverse design for strain fields of hierarchical architectures. Composites Part B 299: 112372. https://doi.org/10.1016/j.compositesb.2025.112372
[21]	Sechkar K, Steel H (2025) Model-guided gene circuit design for engineering genetically stable cell populations in diverse applications. J R Soc Interface 22: 20240602. https://doi.org/10.1098/rsif.2024.0602
[22]	Shen H, Zhang C, Li S, et al. (2024) Prodrug-conjugated tumor-seeking commensals for targeted cancer therapy. Nat Commun 15: 4343. https://doi.org/10.1038/s41467-024-48661-y
[23]	Yang S, Sheffer M, Kaplan IE, et al. (2025) Non-pathogenic E. coli displaying decoy-resistant IL18 mutein boosts anti-tumor and CAR NK cell responses. Nat Biotechnol 43: 1311-1323. https://doi.org/10.1038/s41587-024-02418-6
[24]	Tumas S, Meldgaard TS, Vaaben TH, et al. (2023) Engineered E. coli Nissle 1917 for delivery of bioactive IL-2 for cancer immunotherapy. Sci Rep 13: 12506. https://doi.org/10.1038/s41598-023-39365-2
[25]	Tanniche I, Behkam B (2023) Engineered live bacteria as disease detection and diagnosis tools. J Biol Eng 17: 65. https://doi.org/10.1186/s13036-023-00379-z
[26]	Fdez-Sanromán A, Bernárdez-Rodas N, Rosales E, et al. (2025) Biosensor technologies for water quality: detection of emerging contaminants and pathogens. Biosensors 15: 189. https://doi.org/10.3390/bios15030189
[27]	Vojnovic S, Aleksic I, Ilic-Tomic T, et al. (2024) Bacillus and Streptomyces spp. as hosts for production of industrially relevant enzymes. Appl Microbiol Biotechnol 108: 185. https://doi.org/10.1007/s00253-023-12900-x
[28]	Wang Y, Wang Q, Sha A, et al. (2023) Advances in synthetic biology techniques and industrial applications of Corynebacterium glutamicum. Fermentation 9: 729. https://doi.org/10.3390/fermentation9080729
[29]	Krysenko S (2025) Current approaches for genetic manipulation of Streptomyces spp.—key bacteria for biotechnology and environment. BioTech 14: 3. https://doi.org/10.3390/biotech14010003
[30]	Zalila-Kolsi I, Al-Barazie R (2025) Advancing sustainable practices with Paenibacillus polymyxa: From soil health to medical applications and molecular engineering. AIMS Microbiol 11: 338-368. https://doi.org/10.3934/microbiol.2025016
[31]	Iqbal T, Murugan S, Das D (2024) A chimeric membrane enzyme and an engineered whole-cell biocatalyst for efficient 1-alkene production. Sci Adv 10: eadl2492. https://doi.org/10.1126/sciadv.adl2492
[32]	Chae TU, Choi SY, Ahn DH, et al. (2025) Biosynthesis of poly(ester amide)s in engineered Escherichia coli. Nat Chem Biol 21: 1171-1181. https://doi.org/10.1038/s41589-025-01842-2
[33]	Riaz A, Ahmad S, Bibi A, et al. (2025) Process engineering for sustainable bioplastic production using bacillus cereus ard-03 and agricultural biomass. Waste Biomass Valor . https://doi.org/10.1007/s12649-025-03214-2
[34]	Sharma S, Pathania S, Bhagta S, et al. (2024) Microbial remediation of polluted environment by using recombinant E. coli: a review. Biotechnol Environ 1: 8. https://doi.org/10.1186/s44314-024-00008-z
[35]	Ruan G, Mi W, Yin X, et al. (2022) Molecular responses mechanism of Synechocystis sp. PCC 6803 to cadmium stress. Water 14: 4032. https://doi.org/10.3390/w14244032
[36]	Dutto A, Kan A, Saraw Z, et al. (2025) Living porous ceramics for bacteria-regulated gas sensing and carbon capture. Adv Mater 37: 2412555. https://doi.org/10.1002/adma.202412555
[37]	Ortiz-Medina JF, Poole MR, Grunden AM, et al. (2023) Nitrogen fixation and ammonium assimilation pathway expression of geobacter sulfurreducens changes in response to the anode potential in microbial electrochemical cells. Appl Environ Microbiol 89: e02073-22. https://doi.org/10.1128/aem.02073-22
[38]	Rocco DHE, Freire BM, Oliveira TJ, et al. (2024) Bacillus subtilis as an effective tool for bioremediation of lead, copper and cadmium in water. Discov Appl Sci 6: 430. https://doi.org/10.1007/s42452-024-06101-y
[39]	Zeng Y, Wang M, Yu Y, et al. (2024) Rice N-biofertilization by inoculation with an engineered photosynthetic diazotroph. World J Microbiol Biotechnol 40: 136. https://doi.org/10.1007/s11274-024-03956-6
[40]	Dal Cortivo C, Ferrari M, Visioli G, et al. (2020) Effects of seed-applied biofertilizers on rhizosphere biodiversity and growth of common wheat (Triticum aestivum L.) in the field. Front Plant Sci 11: 72. https://doi.org/10.3389/fpls.2020.00072
[41]	Su P, Kang H, Peng Q, et al. (2024) Microbiome homeostasis on rice leaves is regulated by a precursor molecule of lignin biosynthesis. Nat Commun 15: 23. https://doi.org/10.1038/s41467-023-44335-3
[42]	Zalila-Kolsi I, Sellami S, Tounsi S, et al. (2018) Heterologous expression and periplasmic secretion of an antifungal Bacillus amyloliquefaciens BLB 369 endo-β-1,3-1,4-glucanase in Escherichia coli. Journal of Phytopathology 166: 28-33. https://doi.org/10.1111/jph.12656
[43]	Azizoglu U, Jouzani GS, Yilmaz N, et al. (2020) Genetically modified entomopathogenic bacteria, recent developments, benefits and impacts: A review. Sci Total Environ 734: 139169. https://doi.org/10.1016/j.scitotenv.2020.139169
[44]	Sagar A, Yadav SS, Sayyed RZ, et al. (2022) Bacillus subtilis: A multifarious plant growth promoter, biocontrol agent, and bioalleviator of abiotic stress. Bacilli in Agrobiotechnology . Springer International Publishing 561-580. https://doi.org/10.1007/978-3-030-85465-2_24
[45]	Lee JH, Cheon IS, Shim BS, et al. (2012) Draft genome sequence of Klebsiella pneumoniae subsp. pneumoniae DSM 30104^T. J Bacteriol 194: 5722-5723. https://doi.org/10.1128/JB.01388-12
[46]	Rottinghaus AG, Ferreiro A, Fishbein SRS, et al. (2022) Genetically stable CRISPR-based kill switches for engineered microbes. Nat Commun 13: 672. https://doi.org/10.1038/s41467-022-28163-5
[47]	Peri I, Consentino F, Grasso A, et al. (2025) Integrating societal concern into an EU regulatory proposal for new genomic techniques in food crops using association rules. Agric & Food Secur 14: 18. https://doi.org/10.1186/s40066-025-00539-y
[48]	U.S. Food and Drug AdministrationEarly clinical trials with live biotherapeutic products: Chemistry, manufacturing, and control information; guidance for industry (2016).
[49]	National Institutes of HealthNIH guidelines for research involving recombinant or synthetic nucleic acid molecules (2024).
[50]	Pharmaceuticals and Medical Devices Agency, Japanct on the conservation and sustainable use of biological diversity through regulations on the use of living modified organisms (Cartagena Act) (2003).
[51]	Shenzhen Municipal GovernmentRegulations on promoting the innovative development of the synthetic biology industry in the shenzhen special economic zone (2025).
[52]	Johnson AL, George DR, Matthews KRW, et al. The regulatory landscape for synthetic biology, baker institute for public policy, Rice University (2025).
[53]	Ingram D, Stan GB (2023) Modelling genetic stability in engineered cell populations. Nat Commun 14: 3471. https://doi.org/10.1038/s41467-023-38850-6
[54]	Alamnie G, Andualem B (2020) Biosafety issues of unintended horizontal transfer of recombinant DNA. Genetic Transformation in Crops . IntechOpen. https://doi.org/10.5772/intechopen.93170
[55]	Lux MW, Strychalski EA, Vora GJ (2023) Special issue: reproducibility in synthetic biology. Synth Biol 8: ysad015. https://doi.org/10.1093/synbio/ysad015
[56]	Cubillos-Ruiz A, Guo T, Sokolovska A, et al. (2021) Engineering living therapeutics with synthetic biology. Nat Rev Drug Discov 20: 941-960. https://doi.org/10.1038/s41573-021-00285-3
[57]	Chen YC, Destouches L, Cook A, et al. (2024) Synthetic microbial ecology: engineering habitats for modular consortia. J Appl Microbiol 135: lxae158. https://doi.org/10.1093/jambio/lxae158
[58]	Cai Q, Guo R, Chen D, et al. (2025) SynBioNanoDesign: pioneering targeted drug delivery with engineered nanomaterials. J Nanobiotechnol 23: 178. https://doi.org/10.1186/s12951-025-03254-9
[59]	Nguyen DH, Chong A, Hong Y, et al. (2023) Bioengineering of bacteria for cancer immunotherapy. Nat Commun 14: 3553. https://doi.org/10.1038/s41467-023-39224-8
[60]	Nazir A, Hussain FHN, Raza A (2024) Advancing microbiota therapeutics: the role of synthetic biology in engineering microbial communities for precision medicine. Front Bioeng Biotechnol 12: 1511149. https://doi.org/10.3389/fbioe.2024.1511149

Reader Comments

Your name:*

Email:*
© 2025 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)