Genetic engineering of probiotic Escherichia coli Nissle 1917 for clinical application

Ou, Bingming; Yang, Ying; Tham, Wai Liang; Chen, Lin; Guo, James C. Y.; Zhu, Guoqiang

doi:10.1007/s00253-016-7829-5

Cited by 88 publications

(76 citation statements)

References 50 publications

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“…Thus, EcN can be used as an engineerable host for genetic manipulation of gut inhabitants, that is, Bifidobacteria , Bacteroides , and LABs. These types of genetic circuits with promoters will provide novel opportunities to explore the potent microbes as probiotic . Some other synthetically engineered probiotics with their significances in therapeutics are enlisted in Table .…”

Section: Synthetic Biology For the Study Of Host–microbe Interactionsmentioning

confidence: 99%

Efficient engineered probiotics using synthetic biology approaches: A review

Yadav

Shukla

2019

Biotech and App Biochem

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The uses of probiotics‐based food supplements are getting emphasis due to their power to ensure better health conditions. Probiotics have diverse and significant applications in the health sector, so probiotic strains require an understanding of the genome level organizations. Probiotics elucidate various functional parameters that control their metabolic functions. In this review, we have compiled aspects of synthetic biology, which are used for the optimization of metabolic processes in probiotics for their use as a supplement in allopathic medicines. Synthetic biology approaches provide information about diverse biosynthetic pathways and also facilitate the novel metabolic engineering approaches for probiotics strain improvement. We have discussed the synthetic biology approaches for producing engineered probiotics via genetic circuits, expression systems, and genome editing tools like CRISPR–Cas and PEVLAB. This review also enlightens future challenges in the development of engineered probiotics.

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Section: Synthetic Biology For the Study Of Host–microbe Interactionsmentioning

confidence: 99%

Efficient engineered probiotics using synthetic biology approaches: A review

Yadav

Shukla

2019

Biotech and App Biochem

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“…Mutaflor® to treat chronic inflammatory and infectious intestinal diseases and is used significantly in the development of microbial therapeutics 16,[64][65][66][67][68][69] . Though there are conflicting reports whether EcN can persist in human intestines 68,70 , it has been shown to colonize the porcine intestinal tract 71 .…”

Section: Escherichia Coli Nissle 1917 (Ecn) Is An Extensively Studiedmentioning

confidence: 99%

Quantifying and engineering mucus adhesion of probiotics

Mays

Chappell

Nair

2019

Preprint

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Mucus in the gastrointestinal (GI) tract is the primary point-of-interaction between humans and their gut microbiota. This not only intimates that mucus ensures protection against endogenous and exogenous opportunists but provision for the human microbiota to reside and flourish. With the emergence of living therapeutics, engineered microbes can deliver and produce increasingly complex medicine, and controlling the mucoadhesive properties of different microbial chassis can dictate dose-response in a patient. Here we present a redesigned, in vitro, plate-based assay to measure the mucus adhesion of various probiotics. Cell-mucus interactions were isolated by immobilizing mucus to the plate surface. Binding parameters were derived for each probiotic strain by measuring cell adhesion over a wide range of cell concentrations, providing dose-dependent adhesion metrics. Surface proteins and cell components known to influence mucoadhesion were then heterologously expressed or altered in Lactococcus lactis MG1363 and E. coli Nissle 1917 to control mucus-binding capacity, avidity, and cooperativity.

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“…In studies using IBD model animals, EcN was proven to ameliorate colitis symptoms by regulation of the immune system and intestinal barrier function (108–111). In addition, the utility of this immunobiotic strain as a production platform for vaccines and pharmaceutics and as an intestinal delivery system continues to grow (112). Studies of gm-EcN that produces pathogenic bacteria/virus antigens (113–115) and immunomodulatory molecules such as cytokines and proteins derived from parasites (24, 25) have been reported, and disease preventive/curative effects have been verified in animals.…”

Section: Escherichia Coli Nissle 1917mentioning

confidence: 99%

Applications of Genetically Modified Immunobiotics with High Immunoregulatory Capacity for Treatment of Inflammatory Bowel Diseases

Shigemori

Shimosato

2017

Front. Immunol.

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Inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn’s disease, are chronic inflammatory diseases characterized by dysregulated immune responses of the gastrointestinal tract. In recent years, the incidence of IBDs has increased in developed nations, but their prophylaxis/treatment is not yet established. Site-directed delivery of molecules showing anti-inflammatory properties using genetically modified (gm)-probiotics shows promise as a new strategy for the prevention and treatment of IBD. Advantages of gm-probiotics include (1) the ability to use bacteria as a delivery vehicle, enabling safe and long-term use by humans, (2) decreased risks of side effects, and (3) reduced costs. The intestinal delivery of anti-inflammatory proteins such as cytokines and enzymes using Lactococcus lactis has been shown to regulate host intestinal homeostasis depending on the delivered protein-specific machinery. Additionally, clinical experience using interleukin 10-secreting Lc. lactis has been shown to be safe and to facilitate biological containment in IBD therapy. On the other hand, some preclinical studies have demonstrated that gm-strains of immunobiotics (probiotic strains able to beneficially regulate the mucosal immunity) provide beneficial effects on intestinal inflammation as a result of the synergy between the immunoregulatory effects of the bacterium itself and the anti-inflammatory effects of the delivered recombinant proteins. In this review, we discuss the rapid progression in the development of strategies for the prophylaxis and treatment of IBD using gm-probiotics that exhibit immune regulation effects (gm-immunobiotics). In particular, we discuss the type of strains used as delivery agents.

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Genetic engineering of probiotic Escherichia coli Nissle 1917 for clinical application

Cited by 88 publications

References 50 publications

Efficient engineered probiotics using synthetic biology approaches: A review

Efficient engineered probiotics using synthetic biology approaches: A review

Quantifying and engineering mucus adhesion of probiotics

Applications of Genetically Modified Immunobiotics with High Immunoregulatory Capacity for Treatment of Inflammatory Bowel Diseases

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