Functional genetics of human gut commensal Bacteroides thetaiotaomicron reveals metabolic requirements for growth across environments
Abstract
Harnessing the microbiota for beneficial outcomes is limited by our poor understanding of the constituent bacteria, as the functions of most of their genes are unknown. Here, we measure the growth of a barcoded transposon mutant library of the gut commensal Bacteroides thetaiotaomicron on 48 carbon sources, in the presence of 56 stress-inducing compounds, and during mono-colonization of gnotobiotic mice. We identify 516 genes with a specific phenotype under only one or a few conditions, enabling informed predictions of gene function. For example, we identify a glycoside hydrolase important for growth on type I rhamnogalacturonan, a DUF4861 protein for glycosaminoglycan utilization, a 3-keto-glucoside hydrolase for disaccharide utilization, and a tripartite multidrug resistance system specifically for bile salt tolerance. Furthermore, we show that B. thetaiotaomicron uses alternative enzymes for synthesizing nitrogen-containing metabolic precursors based on ammonium availability and that these enzymes are used differentially in vivo in a diet-dependent manner.
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Laboratory Directed Research and Development (LDRD) Program
- OSTI Identifier:
- 1768684
- Alternate Identifier(s):
- OSTI ID: 1813358
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Published Article
- Journal Name:
- Cell Reports
- Additional Journal Information:
- Journal Name: Cell Reports Journal Volume: 34 Journal Issue: 9; Journal ID: ISSN 2211-1247
- Publisher:
- Elsevier
- Country of Publication:
- Netherlands
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Bacteroides thetaiotaomicron; random barcode transposon-site sequencing; polysaccharide utilization; bile salts
Citation Formats
Liu, Hualan, Shiver, Anthony L., Price, Morgan N., Carlson, Hans K., Trotter, Valentine V., Chen, Yan, Escalante, Veronica, Ray, Jayashree, Hern, Kelsey E., Petzold, Christopher J., Turnbaugh, Peter J., Huang, Kerwyn Casey, Arkin, Adam P., and Deutschbauer, Adam M. Functional genetics of human gut commensal Bacteroides thetaiotaomicron reveals metabolic requirements for growth across environments. Netherlands: N. p., 2021.
Web. doi:10.1016/j.celrep.2021.108789.
Liu, Hualan, Shiver, Anthony L., Price, Morgan N., Carlson, Hans K., Trotter, Valentine V., Chen, Yan, Escalante, Veronica, Ray, Jayashree, Hern, Kelsey E., Petzold, Christopher J., Turnbaugh, Peter J., Huang, Kerwyn Casey, Arkin, Adam P., & Deutschbauer, Adam M. Functional genetics of human gut commensal Bacteroides thetaiotaomicron reveals metabolic requirements for growth across environments. Netherlands. https://doi.org/10.1016/j.celrep.2021.108789
Liu, Hualan, Shiver, Anthony L., Price, Morgan N., Carlson, Hans K., Trotter, Valentine V., Chen, Yan, Escalante, Veronica, Ray, Jayashree, Hern, Kelsey E., Petzold, Christopher J., Turnbaugh, Peter J., Huang, Kerwyn Casey, Arkin, Adam P., and Deutschbauer, Adam M. Mon .
"Functional genetics of human gut commensal Bacteroides thetaiotaomicron reveals metabolic requirements for growth across environments". Netherlands. https://doi.org/10.1016/j.celrep.2021.108789.
@article{osti_1768684,
title = {Functional genetics of human gut commensal Bacteroides thetaiotaomicron reveals metabolic requirements for growth across environments},
author = {Liu, Hualan and Shiver, Anthony L. and Price, Morgan N. and Carlson, Hans K. and Trotter, Valentine V. and Chen, Yan and Escalante, Veronica and Ray, Jayashree and Hern, Kelsey E. and Petzold, Christopher J. and Turnbaugh, Peter J. and Huang, Kerwyn Casey and Arkin, Adam P. and Deutschbauer, Adam M.},
abstractNote = {Harnessing the microbiota for beneficial outcomes is limited by our poor understanding of the constituent bacteria, as the functions of most of their genes are unknown. Here, we measure the growth of a barcoded transposon mutant library of the gut commensal Bacteroides thetaiotaomicron on 48 carbon sources, in the presence of 56 stress-inducing compounds, and during mono-colonization of gnotobiotic mice. We identify 516 genes with a specific phenotype under only one or a few conditions, enabling informed predictions of gene function. For example, we identify a glycoside hydrolase important for growth on type I rhamnogalacturonan, a DUF4861 protein for glycosaminoglycan utilization, a 3-keto-glucoside hydrolase for disaccharide utilization, and a tripartite multidrug resistance system specifically for bile salt tolerance. Furthermore, we show that B. thetaiotaomicron uses alternative enzymes for synthesizing nitrogen-containing metabolic precursors based on ammonium availability and that these enzymes are used differentially in vivo in a diet-dependent manner.},
doi = {10.1016/j.celrep.2021.108789},
journal = {Cell Reports},
number = 9,
volume = 34,
place = {Netherlands},
year = {Mon Mar 01 00:00:00 EST 2021},
month = {Mon Mar 01 00:00:00 EST 2021}
}
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