Clostridium beijerinckii as Next Generation Probiotics

Both wild-type and genetically engineered Clostridium beijerinckii can be used to achieve tumor-specific drug activation, which is an innovative approach for cancer therapy. Based on our advanced technology platforms and extensive experience, Creative Biolabs has won a good reputation for accomplishing challenging C. beijerinckii based drug discovery projects for our customers all over the world.

Introduction of Clostridium beijerinckii

Clostridium beijerinckii is a gram-positive, rod-shaped, motile bacterium of the genus Clostridium. It exhibits peritrichous flagella. C. beijerinckii species are ubiquitous and routinely isolated from soil samples. It produces oval to subterminal spores, and the morphology of the cell changes over the growth cycle of the organism. Obligate anaerobes C. beijerinckii employs hypoxic germination. C. beijerinckii is the industrially valuable nonpathogenic species of the genus Clostridium.

Clostridium beijerinckii for Cancer Therapy

Despite substantial investment in prevention, treatment, and aftercare, cancer remains a leading cause of death worldwide. A potential solution is the use of endospore-forming Clostridium species such as C beijerinckii, either on their own or as a tumor delivery vehicle for anti-cancer drugs. Clostridium species of anaerobic bacteria thrive and consume oxygen-poor cancerous tissue, whereas dying when they come in contact with the tumor's oxygenated sides. Clostridial spores can home in on these niche environments because of their own unique metabolic need, which enables them to utilize the tumor micro milieu and respective tissues for their proliferation. Both wild-type and genetically modified C. beijerinckii have been demonstrated to colonize and destroy solid tumors specifically.

Treatment of tumors with Clostridium. Fig.1 Treatment of tumors with Clostridium. (Paton, 2012)

C. beijerinckii is amenable to genetic manipulation and has successfully been modified to express several enzymes, which activate different prodrugs. C beijerinckii can be successfully engineered to express genes encoding specific bacterial enzymes (cytosine deaminase, nitroreductase), producing more promising antitumor effects. The CD gene is cloned into a Clostridial expression vector and transformed into C. beijerinckii. Corresponding to CD, similar gene therapy approaches are performed using the E. coli NTR gene in C. beijerinckii. Although CDase or NTR are produced intracellularly, the amounts present in the culture supernatants are enough to kill tumor cells in vitro in the presence of the appropriate prodrug. Expression of the NTR gene by Clostridium in vitro enhanced tumor cell death, and NTR activity is detected in tumors following intravenous administration to mice bearing tumors. The antitumor effects of bacterial treatment can be increased by the application of these engineered C. beijerinckii.

Certain species of obligate anaerobic bacteria, such as C. beijerinckii, have been shown to provide tumor specificity for therapy. Based on our deep understanding of C. beijerinckii, Creative Biolabs can provide C. beijerinckii based drug discovery for our customers all over the world. If you want to know more information, please do not hesitate to contact us.

Reference

  1. Paton, A.W.; et al. Bioengineered microbes in disease therapy. Trends in molecular medicine. 2012. 18(7), pp.417-425.

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