Engineered bacteria titrate hydrogen sulfide and induce concentration-dependent effects on the host in a gut microphysiological system
Justin A. Hayes,
Anna W. Lunger,
Aayushi S. Sharma,
Matthew T. Fernez,
Rebecca L. Carrier,
Abigail N. Koppes,
Ryan Koppes,
Benjamin M. Woolston
Affiliations
Justin A. Hayes
Department of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA
Anna W. Lunger
Department of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA
Aayushi S. Sharma
Department of Mechanical and Industrial Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA; Department of Bioengineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA
Matthew T. Fernez
Department of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA
Rebecca L. Carrier
Department of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA; Department of Bioengineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA; Department of Biology, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA
Abigail N. Koppes
Department of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA; Department of Bioengineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA
Ryan Koppes
Department of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA; Corresponding author
Benjamin M. Woolston
Department of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA; Corresponding author
Summary: Hydrogen sulfide (H2S) is a gaseous microbial metabolite whose role in gut diseases is debated, with contradictory results stemming from experimental difficulties associated with accurate dosing and measuring H2S and the use of model systems that do not accurately represent the human gut environment. Here, we engineer Escherichia coli to titrate H2S across the physiological range in a gut microphysiological system (chip) supportive of the co-culture of microbes and host cells. The chip is engineered to maintain H2S gas tension and enables visualization of co-culture in real time with confocal microscopy. Engineered strains colonize the chip and are metabolically active for 2 days, during which they produce H2S across a 16-fold range and induce changes in host gene expression and metabolism in an H2S-concentration-dependent manner. These results validate a platform for studying the mechanisms underlying microbe-host interactions by enabling experiments that are infeasible with current animal and in vitro models.
