Genetically Engineered Microorganisms and Their Impact on Human Health

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.