ACS Synth Biol
Lab of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Meilong RD 130, Shanghai 200237, China.
Published: November 2023
The emergence of genetically engineered bacteria has provided a new means for the diagnosis and treatment of diseases. However, in vivo applications of these engineered bacteria are hindered by their inefficient accumulation in areas of inflammation. In this study, we constructed an engineered () for directional migration toward tetrathionate (a biomarker of gut inflammation), which is regulated by the TtrSR two-component system (TCS) from OS195 (). Specifically, we removed endogenous to control the motility of . Moreover, we introduced the reductase gene cluster () from typhimurium (), a major pathogen causing gut inflammation, into to metabolize tetrathionate. The resulting strain was tested for its motility along the gradients of tetrathionate; the engineered strain exhibits tropism to tetrathionate compared with the original strain. Furthermore, the engineered could only restore its smooth swimming ability when tetrathionate existed. With these modifications enabling tetrathionate-mediated chemotactic and metabolizing activity, this strategy with therapeutic elements will provide a great potential opportunity for target treatment of various diseases by swapping the corresponding genetic circuits.
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http://dx.doi.org/10.1021/acssynbio.3c00445 | DOI Listing |
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