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Engineered bacteria titrate hydrogen sulfide and induce concentration-dependent effects on host in a gut microphysiological system.


ABSTRACT: Hydrogen sulfide (H2S) is a gaseous microbial metabolite whose role in gut diseases is debated, largely due to the difficulty in controlling its concentration and the use of non-representative model systems in previous work. Here, we engineered E. coli to titrate H2S controllably across the physiological range in a gut microphysiological system (chip) supportive of the co-culture of microbes and host cells. The chip was designed to maintain H2S gas tension and enable visualization of co-culture in real-time with confocal microscopy. Engineered strains colonized the chip and were metabolically active for two days, during which they produced H2S across a sixteen-fold range and induced changes in host gene expression and metabolism in an H2S concentration-dependent manner. These results validate a novel platform for studying the mechanisms underlying microbe-host interactions, by enabling experiments that are infeasible with current animal and in vitro models.

SUBMITTER: Hayes JA 

PROVIDER: S-EPMC10245736 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Engineered bacteria titrate hydrogen sulfide and induce concentration-dependent effects on host in a gut microphysiological system.

Hayes Justin A JA   Lunger Anna W AW   Sharma Aayushi S AS   Fernez Matthew T MT   Koppes Abigail N AN   Koppes Ryan R   Woolston Benjamin M BM  

bioRxiv : the preprint server for biology 20230516


Hydrogen sulfide (H<sub>2</sub>S) is a gaseous microbial metabolite whose role in gut diseases is debated, largely due to the difficulty in controlling its concentration and the use of non-representative model systems in previous work. Here, we engineered <i>E. coli</i> to titrate H<sub>2</sub>S controllably across the physiological range in a gut microphysiological system (chip) supportive of the co-culture of microbes and host cells. The chip was designed to maintain H<sub>2</sub>S gas tension  ...[more]

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