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Optogenetic control of gut bacterial metabolism

Lucas A. Hartsough, Matthew V. Kotlajich, Bing Han, Chih-Chun J. Lin, Lauren Gambill, View ORCID ProfileMeng C. Wang, View ORCID ProfileJeffrey J. Tabor
doi: https://doi.org/10.1101/2020.02.25.964866
Lucas A. Hartsough
1Department of Bioengineering, Rice University, Houston, TX
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Matthew V. Kotlajich
1Department of Bioengineering, Rice University, Houston, TX
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Bing Han
3Huffington Center on Aging, Baylor College of Medicine, Houston, TX
7Children’s Hospital & Institutes of Biomedical Sciences, Fudan University, Shanghai, China, 201102
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Chih-Chun J. Lin
3Huffington Center on Aging, Baylor College of Medicine, Houston, TX
4Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX
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Lauren Gambill
2Systems, Synthetic, and Physical Biology Program, Rice University, Houston, TX
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Meng C. Wang
3Huffington Center on Aging, Baylor College of Medicine, Houston, TX
4Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX
5Howard Hughes Medical Institute
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  • For correspondence: wmeng@bcm.edu jeff.tabor@rice.edu
Jeffrey J. Tabor
1Department of Bioengineering, Rice University, Houston, TX
2Systems, Synthetic, and Physical Biology Program, Rice University, Houston, TX
6Department of Biosciences, Rice University
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  • ORCID record for Jeffrey J. Tabor
  • For correspondence: wmeng@bcm.edu jeff.tabor@rice.edu
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Abstract

Gut bacteria produce a wide range of metabolites that impact host biology. However, in situ studies of microbe-host interactions are challenging due to the poor accessibility of the gut environment. Here, we develop a method wherein light is used to remotely control E. coli gene expression in the C. elegans gastrointestinal tract. We go on to engineer an E. coli strain from which secretion of the longevity-enhancing exopolysaccharide colanic acid (CA) is regulated by light. We then combine this strain with our optogenetic method to discover that CA produced by gut bacteria protects intestinal mitochondria from stress-induced hyper-fragmentation. Finally, we exploit the quantitative control of CA secretion afforded by light to reveal that CA extends worm lifespan in a dose-dependent manner. Optogenetic control of gut bacterial metabolism will enable new mechanistic studies of how the microbiome impacts health and disease.

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Posted February 26, 2020.
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Optogenetic control of gut bacterial metabolism
Lucas A. Hartsough, Matthew V. Kotlajich, Bing Han, Chih-Chun J. Lin, Lauren Gambill, Meng C. Wang, Jeffrey J. Tabor
bioRxiv 2020.02.25.964866; doi: https://doi.org/10.1101/2020.02.25.964866
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Optogenetic control of gut bacterial metabolism
Lucas A. Hartsough, Matthew V. Kotlajich, Bing Han, Chih-Chun J. Lin, Lauren Gambill, Meng C. Wang, Jeffrey J. Tabor
bioRxiv 2020.02.25.964866; doi: https://doi.org/10.1101/2020.02.25.964866

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