Heterologous Expression of NoxA Confers Aerotolerance in Clostridium sporogenes

Abstract

AbstractClostridium is a genus of Gram-positive obligate anaerobic bacteria. Some species of Clostridium, including C. 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 because of higher oxygen levels rise 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 C. aminovalericum. NoxA is a water-forming NADH oxidase enzyme. Thus, its activity 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.