Engineering Bifidobacterium bifidum Services for Live Biotherapeutics Drug Discovery
Background Services FAQs Published Data Resources
Background
One of the main benefits of using probiotics as live carriers to deliver bioactive cytokines is the combination of the inherently beneficial properties of certain strains with the potential effects of delivering proteins. Recombinant probiotics produce specific proteins that have the potential to treat IBD and are currently being considered as new drug alternatives. Bifidobacterium bifidum (B. bifidum) is the second prominent species found in breastfed infants. Although it is beneficial to host health, recombinant Bifidobacterium has only recently been developed because it is limited as a transgenic bacterium due to its strict anaerobic metabolism, multilayered complex cell wall, and restrictive modification system. Because certain strains have recognized probiotic properties, Bifidobacterium is an excellent candidate for developing living vectors to produce and deliver xenoproteins on mucosal surfaces.
Scientists have developed a system for delivering healthy proteins through recombinant Bifidobacterium, called BEST, based on a broad-host-range plasmid pWV01, a dnaK promoter from the dnaK operon of B. bifidum, and two different signaling peptides (SPs). By cloning mouse IL-10 cytokines, the function of the BEST system was validated and its correct expression and biological activity was confirmed in a mouse model of low-grade intestinal inflammation, thereby confirming its potential to deliver therapeutic molecules in the colon. 1, 3
Engineering Bifidobacterium bifidum Services
Services
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Gene knock-out
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Gene knock-in/Gene insertion
Deliverables
Engineered strain in glycerol stock
Quality Control
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Sequencing Validation
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Western Blot Validation (Optional)
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PAGE
or cell-based assay of your interest.
Delivery Time
Starting from 4-6 weeks.
Materials from Clients
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Overall construction scheme.
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Host strain.
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Target gene name.
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Target gene sequence. (if the whole genome sequence is unavailable.)
Frequently Asked Questions
What genetically modified strains of B. bifidum have been developed?
Several genetically modified strains of
B.
bifidum have been studied:
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BGN4-SK: This strain expresses the streptococcal superoxide dismutase (SOD) gene and lactobacillus catalase (CAT) gene, which help in ameliorating inflammatory bowel disease (IBD) by reducing oxidative stress and inflammation.
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BGN4-pBESIL10: Engineered to produce human interleukin-10 (IL-10), this strain aims to exert anti-inflammatory effects, although its efficacy in alleviating colitis was limited compared to BGN4-SK.
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BS42 with BEST system: This strain produced and delivered IL-10, which has an improved effect in a mouse model of low-grade intestinal inflammation.
These strains demonstrate the potential of genetically modified
B.
bifidum in therapeutic applications, particularly in managing gastrointestinal disorders.
1, 2, 3
Published Data
A recombinant Bifidobacterium bifidum BGN4 strain expressing the streptococcal superoxide dismutase gene ameliorates inflammatory bowel disease2, 3
Abstract
In this study, two strains of recombinant B. bifidum were constructed, B. bifidum BGN4-SK strain and BGN4-pBESIL10 strain. The former strains produced antioxidant enzymes, streptococcus superoxide dismutase (SOD) and lactoperoxidase (CAT), while the latter produced the anti-inflammatory cytokine human interleukin (IL) -10. The results showed that recombinant B. bifidum BGN4-SK could improve DSS-induced colitis. Both Bifidobacterium BGN4-SK and Bifidobacterium BGN4-pBESIL10 can reduce the inflammatory level of HT-29 cells. Therefore, B. bifidum BGN4-SK is a potential candidate drug for the treatment of IBD.
Fig.1 Effects of B. bifidum BGN4-SK, BGN4-pBESIL10 or their combination on clinical symptoms in DSS-induced colitis model.2,3
Resources
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References
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Mauras, Aurélie, et al. "A new Bifidobacteria expression system (BEST) to produce and deliver interleukin-10 in Bifidobacterium bifidum." Frontiers in microbiology 9 (2018): 3075.
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Kang, Sini, et al. "A recombinant Bifidobacterium bifidum BGN4 strain expressing the streptococcal superoxide dismutase gene ameliorates inflammatory bowel disease." Microbial Cell Factories 21.1 (2022): 113.
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Distributed under Open Access license CC BY 4.0, with modifications.
For Research Use Only. Not intended for use in food manufacturing or medical procedures (diagnostics or therapeutics). Do Not Use in Humans.
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