Engineered bacteria titrate hydrogen sulfide and induce concentration-dependent effects on the host in a gut microphysiological system.
Engineered bacteria titrate hydrogen sulfide and induce concentration-dependent effects on the host in a gut microphysiological system.
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DOI：
10.1016/j.celrep.2023.113481
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发表时间：
2023-12-26
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
硫化氢(H_2S)是一种气态微生物代谢物，其在肠道疾病中的作用存在争议，其结果相互矛盾，原因是与准确计量和测量H_2S相关的实验困难，以及使用不能准确代表人类肠道环境的模型系统。在这里，我们设计了大肠杆菌，在支持微生物和宿主细胞共培养的肠道微生理系统(芯片)中，在整个生理范围内滴定硫化氢。该芯片被设计成保持硫化氢气体的压力，并能够用共聚焦显微镜实时观察共培养情况。工程菌在芯片上定植并代谢活跃2天，在此期间它们产生16倍范围的H_2S，并以H_2S浓度依赖的方式诱导宿主基因表达和代谢的变化。这些结果验证了一个研究微生物-宿主相互作用潜在机制的平台，使目前的动物和体外模型无法进行的实验成为可能。Hayes等人。展示一个平台，询问气体微生物代谢物在低气体渗透性、人性化肠道微生理系统中的因果作用，从而实现对宿主-微生物相互作用的高分辨率分析。大肠杆菌被设计用来滴定硫化氢水平，这会对宿主基因的表达和代谢产生剂量依赖性的影响。
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. Hayes et al. demonstrate a platform to interrogate the causal role of gaseous microbial metabolites in a low-gas-permeable, humanized gut microphysiological system, enabling high-resolution analysis of host-microbe interactions. E. coli was engineered to titrate hydrogen sulfide levels, which induced dose-dependent effects on host gene expression and metabolism.
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影响因子：
3.7
作者：
Earley H;Lennon G;Balfe A;Kilcoyne M;Clyne M;Joshi L;Carrington S;Martin ST;Coffey JC;Winter DC;O'Connell PR
通讯作者：
O'Connell PR
影响因子：
4.4
作者：
Jiang, Yu;Chen, Biao;Yang, Sheng
通讯作者：
Yang, Sheng
DOI：
10.3390/molecules26113321
发表时间：
2021-06-01
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Kurpet K;Głowacki R;Chwatko G
通讯作者：
Chwatko G
DOI：
10.2174/1874285800802010018
发表时间：
2008
期刊：
The open microbiology journal
影响因子：
--
作者：
Cheng H;Donahue JL;Battle SE;Ray WK;Larson TJ
通讯作者：
Larson TJ
影响因子：
7.7
作者：
Kasendra, Magdalena;Luc, Raymond;Karalis, Katia
通讯作者：
Karalis, Katia