Engineered bacteria titrate hydrogen sulfide and induce concentration-dependent effects on host in a gut microphysiological system.
bioRxiv
; 2023 May 16.
Article
en En
| MEDLINE
| ID: mdl-37293009
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.
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1
Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
BioRxiv
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos