Engineering Bifidobacterium spp. Services for Live Biotherapeutics Drug Discovery
Background Services Genetic Tools Applications Resources
Background
Bifidobacterium is a Gram-positive bacterium that has various probiotic functions and has been widely used in food, healthcare, and medical fields. Research reports that live Bifidobacterium spp. have significant independent anti-tumor effects and auxiliary effects against PD-L1 in mouse melanoma, which may be related to anti-tumor T cell responses, indicating the Bifidobacterium spp. have potential applications in human immunotherapy. Probiotic engineering is also adept at combating infections by competing, quorum sensing, or disguising itself as host cells to prevent pathogens, but this often seems to be limited to the gut.
Engineering Bifidobacterium spp. Services
To increase the variety of engineered Bifidobacterium, supplementing or removing certain genes would help develop more suitable probiotics for human hosts. At present, the engineering research of Bifidobacterium mainly focuses on Bifidobacterium longum and Bifidobacterium breve.
Bifidobacterium Used as Engineering Chassis
With advances in genetic engineering technology, probiotics can also show properties of targeted therapy. Probiotics are modified to make them have more targeted therapeutic factors, strengthen their efficacy, and expand the application field. However, the modification of probiotics is mainly based on the understanding of the mechanism of action of probiotics. Some probiotic Bifidobacterium are modified to include other beneficial cell functions and/or remove adverse properties. Many studies have used Bifidobacterium as an engineering chassis, primarily in response to various environmental triggers. These engineered Bifidobacterium have been designed to facilitate a variety of roles such as biosensing, disease treatment, or improved biological processing.
Genetic Tools for Bifidobacteria spp
The genetic tools used to regulate gene expression in Bifidobacterium can be generally divided into promoters, ribosomal binding site (RBS), and termination sequence. The most commonly used constitutive promoters in bifidobacteria were the promoter of gene hup encoding a histone-like protein and the promoter of gene gap encoding glyceraldehyde-3-phosphate dehydrogenase. Synthetic biology techniques for Bifidobacterium have only been developed in recent years, especially the mutagenesis systems. The expansion of gene-editing technologies will further accelerate the synthetic biology applications of Bifidobacterium. The immune system is abundant in Bifidobacterium, which could be repurposed for genome engineering in their native hosts even though it has only been used for strain typing so far. The gene-editing technologies, as well as other selection and counterselection techniques, will not only pave the way to engineer Bifidobacterium with enhanced/tailored probiotic properties but also, in combination with omics technologies, contribute to a better understanding of the molecular mechanisms of action of this health-promoting bacteria.
Applications of Engineered Bifidobacterium
Although wild-type Bifidobacterium has shown many therapeutic applications in treating diseases, they have been endowed with more functions by integrating new pathways or modifying original metabolic pathways and other synthetic biology tools. These engineered Bifidobacterium are widely used in the treatment of inflammatory diseases, as well as in the in situ delivery and production of various anticancer drugs for the treatment of tumors. At present, several genetically engineered strains of Bifidobacterium have been established, which can produce many anti-cancer molecules in one process.
As genetic tools for the manipulation of Bifidobacterium continue to develop, they enable the engineering of bacteria with enhanced/tailored health-promoting functions. These attempts include improving stress tolerance, delivering therapeutic and prophylactic molecules, preventing or treating pathogen infection, eliminating antibiotic resistance or virulence genes, and monitoring and tracking microbes in the host and environment.
Fig.2 Bioengineering Bifidobacteria with enhanced/tailored probiotic properties for food and biomedical applications through the use of various synthetic biology approaches to perform DNA addition, deletion, and modification in the genome.2, 3
Resources
Creative Biolabs offers a comprehensive range of probiotic solutions to customers worldwide. We build advanced technology platforms, combined with the strength of our international team, to provide the highest quality services using the expertise of our team of experts and personalized solutions. Please do not hesitate to contact us for more details to further accelerate your project.
References
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Zuo, Fanglei, and Harold Marcotte. "Advancing mechanistic understanding and bioengineering of probiotic lactobacilli and bifidobacteria by genome editing." Current Opinion in Biotechnology 70 (2021): 75-82.
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Zuo, Fanglei, Shangwu Chen, and Harold Marcotte. "Engineer probiotic bifidobacteria for food and biomedical applications-Current status and future prospective." Biotechnology Advances 45 (2020): 107654.
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Distributed under Open Access license CC BY 4.0, without modification.
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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