Table 2.
Therapeutic effects of genetically modified bacteria including probiotic strains and other bacterial species.
| Engineered microorganisms | Transformation tools (vector)/route of ad | Target | Method | Outcome | Ref |
|---|---|---|---|---|---|
| L. lactis | Plasmid-encoded genes/oral | V. cholerae | Engineered a strain to express the CAI-1 | Inhibition of cholera progression and protection in high-risk populations | [115] |
| L. reuteri | Electrotransformation of plasmid-encoded genes | S. aureus | Engineered L. reuteri to sense AIP-I | Well detection of AIP-I levels and also S. aureus by recombinant L. reuteri | [116] |
| E. coli Nissle 1917 | NA/oral | VRE | Developed an ECN to deliver and produce bacteriocins for killing VRE strains | Reduction of Enterococcus species in intestine | [117] |
| Saccharomyces boulardii | Plasmid-encoded genes transformation/oral | Antibiotic-resistant C. difficile | Engineered a strain to produce antibody to inactivate toxins | Protection against CDI | [118] |
| L. casei | Electrotransformation of plasmid-encoded genes | L. monocytogenes | Engineered L. casei to express the LAP from L. innocua | Prevent infection by competitive adhesion | [119] |
| E. coli Nissle 1917 | Electrotransformation of plasmid-encoded genes/oral | P. aeruginosa | Developed a modified ECN to sense P. aeruginosa and kill | Protection animal model against P. aeruginosa during infection | [120] |
| E. coli strain “SLIC” | Electrotransformation of plasmid-encoded genes/IT and IV | Mouse CRC cell line (CT26)/mouse B-cell lymphoma line | Engineered a probiotic for release of nanobodies targeting PD-L1 and CTLA-4 | Enhancement in tumor treatment and inhibition of tumor cell proliferation | [121] |
| E. coli Nissle 1917 | Heat shock transformation/IV | Stage IV human breast cancer (4T1 tumor) | Engineered NIR light responsive strain as antitumor factor which is based on light responsive nanoparticles | Efficient tumor growth inhibition by well production of TNFα in tumor by NIR light responsive strain | [122] |
| E. coli Nissle 1917 | Electrotransformation of plasmid-encoded genes/IV | Human hepatocellular carcinoma | Design to deliver p53 and Tum-5 proteins to tumor hypoxic area | Growth inhibition of the human hepatoma SMMC-7721 cells and no side effects on animal model | [123] |
| E. coli Nissle 1917 | NA/SC | Mice colon adenocarcinoma | Developed an engineered probiotic to convert ammonia to an antitumor L-arginine | Increase level of L-arginine in tumor region which yielded by conversion of ammonia and significant effect on clearance of tumors | [124] |
| L. lactis | Electrotransformation of plasmid-encoded genes/NAS | Cervical cancer | L. lactis strain engineered to express IL-12 | Production of IL-12 by L. lactis and enhancement of immune response | [125] |
| B. longum | Electrotransformation of plasmid-encoded genes/intragastric | Colon carcinoma cells | B. longum designed to deliver tumstatin (tum) into the solid tumor | Significant antitumor effects | [126] |
| B. longum 105-A | Electrotransformation of plasmid-encoded genes/IV | Lewis lung cancer | B. longum engineered to deliver spectinomycin-resistant gene | Successful gene delivery by B. longum | [127] |
| Lactobacillus reuteri 100-23C | Electrotransformation of plasmid-encoded genes/IP | PKU | Phenylalanine lyase gene cloned into a shuttle vector for expression in L. reuteri | Blood phenylalanine levels in PKU mice model significantly reduced | [128] |
| E. coli Nissle 1917 | Electrotransformation of plasmid-encoded genes/oral | Colitis | Engineered ECN to produce the 3HB in the mice gut | Improvement in the colon characteristics like weight and lengths and proinflammatory cytokines of the gut tissue | [129] |
| E. coli Nissle 1917 | NA | Ulcerative colitis | Developed an EcN as a nanosystem for diagnosis of UC at home based on production of IL-10 | Detection of UC in less than 1 minute | [130] |
| E. coli Nissle 1917 | NA/oral | Obesity | Genetically modified ECN effects on obesity | Well regulation and good effects on obesity | [131] |
| L. gasseri | Electrotransformation of plasmid-encoded genes/oral | Diabetes | Engineered L. gasseri to produce GLP-1 which is needed for changing cells to insulin-producing cells | Sufficient development of insulin-producing cells in the intestine following treatment by L. gasseri secreting GLP-1 | [132] |
| E. coli Nissle 1917 (SYNB1618) | Electrotransformation of plasmid-encoded genes/ | PKU | The genes encoding phenylalanine ammonia lyase and L-amino acid deaminase inserted into the genome of SYNB1618 | SYNB1618 strains had transient colonies in the intestine and consumed phenylalanine in GI They were safe and tolerable |
[133] |
| E. coli strain (SYNB8802) | Electrotransformation of plasmid-encoded genes/ | Primary hyperoxaluria type I | Designed a strain to have ability to hydrolyse oxalic acid in GI | Safety and successful result of treatment Kidney damage reduction caused by hyperoxaluria |
[134] |
| E. coli strain (SYNB1020) | Electrotransformation of plasmid-encoded genes/oral | Hyperammonemia | Design to hydrolyse ammonia into L-arginine | Improvement in the survival of mice | [135] |
| E. coli Nissle 1917 | Electrotransformation of plasmid-encoded genes/oral | IBD | Designed sulfate sensor (ThsSR) and tetrathionate sensor (TtrSR) and transferred them into the ECN | Successful in diagnostics and therapeutics purposes | [136] |
| E. coli NGF-1 | Construct was transformed by transduction/oral | IBD | Engineered E. coli NGF-1 to sense tetrathionate | Well detection of tetrathionate | [137] |
| E. coli Nissle 1917 | Electrotransformation of plasmid-encoded genes | IBD | Engineered an ECN strain to accumulate in desired sites and secrete GM-CSF in presence of NO | Successful movements of bacteria to NO | [138] |
| E. coli Nissle 1917 | Electrotransformation of plasmid-encoded genes/oral | IBD | Designed EcN to produce curli-fused TFFs as fibrous matrices for strength and gut epithelial integrity | EcN produced the curli-fused TFFs and protection against colitis in animal model | [139] |
| E. coli Nissle 1917 (EcN-Sj16) | Electrotransformation of plasmid-encoded genes/IP | IBD | Designed EcN-Sj16 to express Sj16 | Increase in expression of Sj16 in the GI and improvement in symptoms | [140] |
| Yeast strain BS016 | Lithium acetate transformation method/oral | IBD | Designed an engineered yeast to express P2Y2 receptor to sense inflammatory | Inhibition of inflammation induced in IBD | [141] |
| E. coli Nissle 1917 | NA/oral | IBD | Developed a PDNI coating ECN to regulate immune responses and improve gut microflora | Inhibition of excessive immune response and amelioration of colitis symptoms | [1] |
| L. reuteri | Electrotransformation of plasmid-encoded genes | Staphylococcus aureus | Development of a sensor to detect AIP-I and staphylococcal detection | Well and successful detection of AIP-I levels by engineered biosensor | [116] |
| E. coli Nissle 1917 | Plasmid-encoded genes | Pseudomonas aeruginosa | Development of an engineered strain to detect the AHL and kill pathogen | Significant antibacterial activity | [120] |
| Harmless E. coli | Plasmid-encoded genes/oral | Pathogenic infection (enterotoxigenic E. coli) | Synthesis of a heat-labile enterotoxin-binding chimeric LPS with high avidity | Prevent and control diarrhea caused by enterotoxigenic Escherichia coli strains | [142] |
| E. coli | Plasmid-encoded genes | V. cholerae | Engineered a strain to express the Art-085 | Inhibit the growth of V. cholerae by integrated sense and kill system in engineered strain | [143] |
| B.subtilis | Electrotransformation of plasmid-encoded genes/intragastric | Alcoholic liver | Coexpressing scADH and istALDH in food-grade B. subtilis | Alcohol detoxification and liver injury treatment | [144] |
| B. ovatus | Plasmid-encoded genes/oral | IBD | Modified B. ovatus for controlled in situ TGF-1 release and colitis treatment | Improvement in colitis, repair of injured colonic epithelium, decrease in inflammatory cell infiltration, reduction in proinflammatory cytokine expression, stimulation of mucin-rich goblet cell production in colonic crypts | [145] |
| E. coli | Transduction/oral | IBD | Development of an engineered strain to detect tetrathionate, which is produced during inflammation | Tetrathionate detection | [137] |
| S. typhimurium | Plasmid-encoded genes/oral | Cancer | Designed and engineered a clinical bacteria to lyse and release genetic cargo at a threshold population density | Significantly reduced tumor activity by combining chemotherapy and engineering bacteria | [146] |
| S. Typhimurium | N/A/IV | Cancer | Designed the Lux QS system and GFP reporter and transferred them into nonpathogenic Salmonella | Potential way to treat cancer by minimizing off-target therapeutic delivery | [147] |
| S. typhimurium | Electrotransformation of plasmid-encoded genes/intratumoral | Cancer | Stimulation of immune response in tumor tissue by induction of FlaB | Reduced tumor formation and metastasis in animal experiments while increasing survival time | [148] |
| E. coli | Transformation of plasmid-encoded genes/oral | Colitis | Designing invasive and nonpathogenic E. coli (dap) auxotroph, harboring plasmid pGB2Oinv-hly | Reducing the severity of experimental colitis in mice | [149] |
| E. coli | Plasmid-encoded genes/oral | Fever | Use from integration of molecular bioswitches into thermal logic circuits in three in vivo microbial therapeutic scenarios | Detect fever by thermosensitive promoters | [150] |
| E. coli | Electroporation of plasmid-encoded genes | Inflammation and glycosuria | Development of digitization, thresholding circuit, and amplification of nitrogen oxides and glucose in clinical samples | Detection of abnormal glycosuria in diabetes patients' urine using bactosensors | [151] |
| E. coli | Plasmid-encoded genes/IV | Cancer | Designed tumor-specific modular synthetic adhesins to improve targeting | Engineered bacteria with SAs colonize solid tumors with higher efficiency than the wild type of strain | [152] |
| S. typhimurium | Electrotransformation of plasmid-encoded genes/subcutaneous | Cancer | Design of an attenuated strain for IFN-γ secretion and expression | Treatment of melanoma | [153] |
| B. subtilis | Plasmid-encoded genes/oral | H. pylori | Design of H. pylori urease B on the Bacillus subtilis spore coat | Inhibition of H. pylori infection and development of an oral vaccine | [154] |
| S. typhimurium | Electroporation of plasmid-encoded genes/oral | Lyme disease | S. typhimurium strain engineered to expresses OspA | Protected against an intradermal challenge with the spirochete high titers of anti-OspA antibodies | [155] |
| Streptococcus | Plasmid-encoded genes | HIV | The production of an antiviral protein to prevent HIV infection in the vaginal mucosa | Maintaining an effective concentration of a microbicide in the vaginal mucosa by CV-N, an anti-HIV protein found in S. gordonii | [156] |
| E. coli | Transformation of plasmid-encoded genes/oral | V. cholerae | The genes encoding glycosyltransferase from Neisseria gonorrhoeae and Campylobacter inserted into harmless Escherichia coli strain | Toxin-binding probiotics have significant potential for cholera prevention and therapy in humans | [157] |
| Salmonella | Plasmid-encoded genes/intratumoral | Cancer | Designed a strain to have ability to delivery and production of Cp53 peptide | Death of tumor cells | [158] |
ad, administration; EcN, E. coli Nissle 1917; PD-L1, programmed cell death-ligand 1; CTLA-4, cytotoxic T lymphocyte-associated protein-4; CAI-1, cholera autoinducer 1; AIP-I, autoinducer peptide-I; AHL, autoinducer N-acyl homoserine lactone; IT, intratumoral; IV, intravenous; IP, intraperitoneal; NAS, intranasal; CRC, colorectal cancer; PKU, phenylketonuria; CDI, C. difficile infection; NIR; near-infrared; 3HB, 3-hydroxybutyrate; IBD, inflammatory bowel disease; TFFs, trefoil factors; Sj16, schistosome immunoregulatory protein; PDNI, polydopamine nanoparticular immunosuppressant; LAP, Listeria adhesion protein; AIP-I, autoinducer peptide-I; VRE, vancomycin-resistant Enterococcus; UC, ulcerative colitis; LPS, lipopolysaccharide; Art-085, killing protein; B. subtilis, Bacillus subtilis; scADH, alcohol dehydrogenase from Saccharomyces cerevisiae; istALDH; aldehyde dehydrogenase from Issatchenkia terricola; B. ovatus, Bacteroides ovatus; QS, quorum sensing; dap, diaminopimelate; SAs, synthetic adhesins; IFN-γ, interferon-gamma; H. pylori, Helicobacter pylori; OspA, outer surface protein; S. typhimurium, Salmonella typhimurium; P. aeruginosa, Pseudomonas aeruginosa.