Clostridium acetobutylicum as Next Generation Probiotics

Clostridium is the primary obligate anaerobe investigated as an anticancer agent. In the last decade, there has been significant progress in the development and refinement of strategies based on tumor colonization using a range of Clostridium species. Based on our extensive experience, Creative Biolabs provides Clostridium acetobutylicum based drug development for our customers all over the world.

Introduction of Clostridium acetobutylicum

C. acetobutylicum is the industrially valuable nonpathogenic species of Clostridium, which is a group of obligatory anaerobic, Gram-positive endospore-forming bacillus. C. acetobutylicum is most often soil-dwelling, although it has been found in several different environments. C. acetobutylicum demonstrates peritrichous flagella and amylolytic activity. Furthermore, C. acetobutylicum is well characterized by its biphasic fermentative metabolism. C. acetobutylicum is a bacterial species that ferments sugar to a mixture of organic solvents. C. acetobutylicum naturally produces acetone as well as butanol and ethanol.

The general cell cycle of C. acetobutylicum. Fig.1 The general cell cycle of C. acetobutylicum. (Janssen, 2014)

Clostridium acetobutylicum for Cancer Therapy

Based on the engineering of nonpathogenic C. acetobutylicum, the transfer of therapeutic proteins to the hypoxic/necrotic extracellular microenvironment of solid tumors is an effective methodology for cancer therapy. By endowing C. acetobutylicum with a gene that encodes a prodrug-converting enzyme, innocuous prodrugs delivered to the tumor can be converted to highly cytotoxic compounds. Meanwhile, the presence of severe hypoxia and necrosis in solid tumors offers the potential to apply an anaerobic bacterial enzyme/prodrug approach such as C. acetobutylicum in cancer treatment.

C. acetobutylicum can be genetically engineered to express and secrete murine tumor necrosis factor-alpha (TNF-alpha) and rat interleukin-2 (IL-2). Both cytokines could be efficiently secreted and are shown to be biologically active and demonstrated anti-tumor activity. Using the in vivo tumor model, C. acetobutylicum has proved to colonize the tumors, whereas the proliferation of these bacteria is absent in normal tissues.

C. acetobutylicum for cancer therapy. Fig.2 C. acetobutylicum for cancer therapy. (Mengesha, 2007)

By introducing rat IL-2 into C. acetobutylicum, solid tumors are specifically targeted, and sufficient levels of IL2 are produced to decrease tumors in mice while avoiding the effects of systemic toxicity. Results with IL-2-producing C. acetobutylicum intra-tumoural administered are promising because a significant tumor growth delay is observed. Similarly, CD expressed in C. acetobutylicum has demonstrated a selective delivery of the active exogenous enzyme into tumors. Thus, C. acetobutylicum as saccharolytic strains might have therapeutic potential, and the results provide evidence for the potential application of Clostridium-based therapeutic protein transfer to tumors in anticancer therapy.

Based on its colonization pattern and safety, the availability of C. acetobutylicum opens the way to investigate its efficacy in cancer therapy. Creative Biolabs is one of the well-recognized experts who are professional in offering C. acetobutylicum-based drug development for our global customers. If you have any questions, please feel free to contact us for more information.

References

  1. Janssen H.; et al. Clostridium: Clostridium acetobutylicum. Encyclopedia of Food Microbiology: Second Edition. Elsevier Inc. 2014. 449-457.
  2. Mengesha A.; et al. Potential and limitations of bacterial-mediated cancer therapy. Front Biosci. 2007: 3880-3891.
CAT Product Name Product Overview
LBST-066FG Clostridium acetobutylicum; 8008 Clostridium acetobutylicum is a Gram-positive bacillus. It requires anaerobic conditions in order to grow in its vegetative state. In its vegetative states, it is motile via flagella across is entire surface.
LBST-067FG Clostridium acetobutylicum; 8010 Clostridium acetobutylicum is a Gram-positive bacillus. It requires anaerobic conditions in order to grow in its vegetative state. In its vegetative states, it is motile via flagella across is entire surface.
LBST-068FG Clostridium acetobutylicum; 2289 Clostridium acetobutylicum is a chemoorganotroph. It is a Gram-positive bacillus. It requires anaerobic conditions in order to grow in its vegetative state.

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