1. Functional genetics of human gut commensal Bacteroides thetaiotaomicron reveals metabolic requirements for growth across environments.
- Author
-
Liu H, Shiver AL, Price MN, Carlson HK, Trotter VV, Chen Y, Escalante V, Ray J, Hern KE, Petzold CJ, Turnbaugh PJ, Huang KC, Arkin AP, and Deutschbauer AM
- Subjects
- Adaptation, Physiological, Ammonium Compounds metabolism, Animals, Anti-Bacterial Agents metabolism, Bacterial Proteins genetics, Bacterial Proteins metabolism, Bacteroides thetaiotaomicron drug effects, Bacteroides thetaiotaomicron enzymology, Bacteroides thetaiotaomicron growth & development, Bile Acids and Salts metabolism, Databases, Genetic, Disaccharides metabolism, Drug Resistance, Bacterial genetics, Gastrointestinal Microbiome drug effects, Gene Expression Regulation, Bacterial, Glycoside Hydrolases genetics, Glycoside Hydrolases metabolism, Humans, Male, Membrane Transport Proteins genetics, Membrane Transport Proteins metabolism, Mice, Inbred C57BL, Mutation, Substrate Specificity, Tripartite Motif Proteins genetics, Tripartite Motif Proteins metabolism, Mice, Bacteroides thetaiotaomicron genetics, Diet, Energy Metabolism genetics, Gastrointestinal Microbiome genetics, Intestines microbiology
- 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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF