Heterologous expression of NoxA confers aerotolerance in Clostridium sporogenes
- PMID: 37818934
- DOI: 10.1002/biot.202300161
Heterologous expression of NoxA confers aerotolerance in Clostridium sporogenes
Abstract
Clostridium is a genus of gram-positive obligate anaerobic bacteria. Some species of Clostridium, including Clostridium sporogenes, may be of use in bacteria-mediated cancer therapy. Spores of Clostridium are inert in healthy normoxic tissue but germinate when in the hypoxic regions of solid tumors, causing tumor regression. However, such treatments fail to completely eradicate tumors partly because of higher oxygen levels at the tumor's outer rim. In this study, we demonstrate that a degree of aerotolerance can be introduced to C. sporogenes by transfer of the noxA gene from Clostridium aminovalericum. NoxA is a water-forming NADH oxidase enzyme, and so has no detrimental effect on cell viability. In addition to its potential in cancer treatment, the noxA-expressing strain described here could be used to alleviate challenges related to oxygen sensitivity of C. sporogenes in biomanufacturing.
Keywords: C. sporogenes; Clostridia; NADH oxidase; aerotolerance; noxA gene.
© 2023 The Authors. Biotechnology Journal published by Wiley-VCH GmbH.
References
REFERENCES
-
- Kubiak, A. M., Poehlein, A., Budd, P., Kuehne, S. A., Winzer, K., Theys, J., Lambin, P., Daniel, R., & Minton, N. P. (2015). Complete genome sequence of the nonpathogenic soil-dwelling bacterium Clostridium sporogenes strain NCIMB 10696. Genome Announcements, 3, 4-5.
-
- Fox, M. E., Lemmon, M. J., Mauchline, M. L., Davis, T. O., Giaccia, A. J., Minton, N. P., & Brown, J. M. (1996). Anaerobic bacteria as a delivery system for cancer gene therapy: In vitro activation of 5-fluorocytosine by genetically engineered clostridia. Gene Therapy, 3, 173-178.
-
- Kubiak, A. M., & Minton, N. P. (2015). The potential of clostridial spores as therapeutic delivery vehicles in tumour therapy. Research in Microbiology, 166, 244-254.
-
- Mowday, A. M., Guise, C. P., Ackerley, D. F., Minton, N. P., Lambin, P., Dubois, L. J., Theys, J., Smaill, J. B., & Patterson, A. V. (2016). Advancing clostridia to clinical trial: past lessons and recent progress. Cancers (Basel), 8, 63. https://doi.org/10.3390/cancers8070063
-
- Lemmon, M. J., Van Zijl, P., Fox, M. E., Mauchline, M. L., Giaccia, A. J., Minton, N. P., & Brown, J. M. (1997). Anaerobic bacteria as a gene delivery system that is controlled by the tumor microenvironment. Gene Therapy, 4, 791-796.
MeSH terms
Substances
Supplementary concepts
Grants and funding
LinkOut - more resources
Full Text Sources
Medical