Mouse Gut Microbiome-Encoded β-Glucuronidases Identified Using Metagenome Analysis Guided by Protein Structure

ABSTRACT Gut microbial β-glucuronidase (GUS) enzymes play important roles in drug efficacy and toxicity, intestinal carcinogenesis, and mammalian-microbial symbiosis. Recently, the first catalog of human gut GUS proteins was provided for the Human Microbiome Project stool sample database and reveale...

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Autores principales:	Benjamin C. Creekmore, Josh H. Gray, William G. Walton, Kristen A. Biernat, Michael S. Little, Yongmei Xu, Jian Liu, Raad Z. Gharaibeh, Matthew R. Redinbo
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	beta-glucuronidase gut microbiome mouse metagenomics protein structure-function Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b1c52767175148238815600a394ac356
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spelling	oai:doaj.org-article:b1c52767175148238815600a394ac3562021-12-02T19:46:18ZMouse Gut Microbiome-Encoded β-Glucuronidases Identified Using Metagenome Analysis Guided by Protein Structure10.1128/mSystems.00452-192379-5077https://doaj.org/article/b1c52767175148238815600a394ac3562019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00452-19https://doaj.org/toc/2379-5077ABSTRACT Gut microbial β-glucuronidase (GUS) enzymes play important roles in drug efficacy and toxicity, intestinal carcinogenesis, and mammalian-microbial symbiosis. Recently, the first catalog of human gut GUS proteins was provided for the Human Microbiome Project stool sample database and revealed 279 unique GUS enzymes organized into six categories based on active-site structural features. Because mice represent a model biomedical research organism, here we provide an analogous catalog of mouse intestinal microbial GUS proteins—a mouse gut GUSome. Using metagenome analysis guided by protein structure, we examined 2.5 million unique proteins from a comprehensive mouse gut metagenome created from several mouse strains, providers, housing conditions, and diets. We identified 444 unique GUS proteins and organized them into six categories based on active-site features, similarly to the human GUSome analysis. GUS enzymes were encoded by the major gut microbial phyla, including Firmicutes (60%) and Bacteroidetes (21%), and there were nearly 20% for which taxonomy could not be assigned. No differences in gut microbial gus gene composition were observed for mice based on sex. However, mice exhibited gus differences based on active-site features associated with provider, location, strain, and diet. Furthermore, diet yielded the largest differences in gus composition. Biochemical analysis of two low-fat-associated GUS enzymes revealed that they are variable with respect to their efficacy of processing both sulfated and nonsulfated heparan nonasaccharides containing terminal glucuronides. IMPORTANCE Mice are commonly employed as model organisms of mammalian disease; as such, our understanding of the compositions of their gut microbiomes is critical to appreciating how the mouse and human gastrointestinal tracts mirror one another. GUS enzymes, with importance in normal physiology and disease, are an attractive set of proteins to use for such analyses. Here we show that while the specific GUS enzymes differ at the sequence level, a core GUSome functionality appears conserved between mouse and human gastrointestinal bacteria. Mouse strain, provider, housing location, and diet exhibit distinct GUSomes and gus gene compositions, but sex seems not to affect the GUSome. These data provide a basis for understanding the gut microbial GUS enzymes present in commonly used laboratory mice. Further, they demonstrate the utility of metagenome analysis guided by protein structure to provide specific sets of functionally related proteins from whole-genome metagenome sequencing data.Benjamin C. CreekmoreJosh H. GrayWilliam G. WaltonKristen A. BiernatMichael S. LittleYongmei XuJian LiuRaad Z. GharaibehMatthew R. RedinboAmerican Society for Microbiologyarticlebeta-glucuronidasegut microbiomemouse metagenomicsprotein structure-functionMicrobiologyQR1-502ENmSystems, Vol 4, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	beta-glucuronidase gut microbiome mouse metagenomics protein structure-function Microbiology QR1-502
spellingShingle	beta-glucuronidase gut microbiome mouse metagenomics protein structure-function Microbiology QR1-502 Benjamin C. Creekmore Josh H. Gray William G. Walton Kristen A. Biernat Michael S. Little Yongmei Xu Jian Liu Raad Z. Gharaibeh Matthew R. Redinbo Mouse Gut Microbiome-Encoded β-Glucuronidases Identified Using Metagenome Analysis Guided by Protein Structure
description	ABSTRACT Gut microbial β-glucuronidase (GUS) enzymes play important roles in drug efficacy and toxicity, intestinal carcinogenesis, and mammalian-microbial symbiosis. Recently, the first catalog of human gut GUS proteins was provided for the Human Microbiome Project stool sample database and revealed 279 unique GUS enzymes organized into six categories based on active-site structural features. Because mice represent a model biomedical research organism, here we provide an analogous catalog of mouse intestinal microbial GUS proteins—a mouse gut GUSome. Using metagenome analysis guided by protein structure, we examined 2.5 million unique proteins from a comprehensive mouse gut metagenome created from several mouse strains, providers, housing conditions, and diets. We identified 444 unique GUS proteins and organized them into six categories based on active-site features, similarly to the human GUSome analysis. GUS enzymes were encoded by the major gut microbial phyla, including Firmicutes (60%) and Bacteroidetes (21%), and there were nearly 20% for which taxonomy could not be assigned. No differences in gut microbial gus gene composition were observed for mice based on sex. However, mice exhibited gus differences based on active-site features associated with provider, location, strain, and diet. Furthermore, diet yielded the largest differences in gus composition. Biochemical analysis of two low-fat-associated GUS enzymes revealed that they are variable with respect to their efficacy of processing both sulfated and nonsulfated heparan nonasaccharides containing terminal glucuronides. IMPORTANCE Mice are commonly employed as model organisms of mammalian disease; as such, our understanding of the compositions of their gut microbiomes is critical to appreciating how the mouse and human gastrointestinal tracts mirror one another. GUS enzymes, with importance in normal physiology and disease, are an attractive set of proteins to use for such analyses. Here we show that while the specific GUS enzymes differ at the sequence level, a core GUSome functionality appears conserved between mouse and human gastrointestinal bacteria. Mouse strain, provider, housing location, and diet exhibit distinct GUSomes and gus gene compositions, but sex seems not to affect the GUSome. These data provide a basis for understanding the gut microbial GUS enzymes present in commonly used laboratory mice. Further, they demonstrate the utility of metagenome analysis guided by protein structure to provide specific sets of functionally related proteins from whole-genome metagenome sequencing data.
format	article
author	Benjamin C. Creekmore Josh H. Gray William G. Walton Kristen A. Biernat Michael S. Little Yongmei Xu Jian Liu Raad Z. Gharaibeh Matthew R. Redinbo
author_facet	Benjamin C. Creekmore Josh H. Gray William G. Walton Kristen A. Biernat Michael S. Little Yongmei Xu Jian Liu Raad Z. Gharaibeh Matthew R. Redinbo
author_sort	Benjamin C. Creekmore
title	Mouse Gut Microbiome-Encoded β-Glucuronidases Identified Using Metagenome Analysis Guided by Protein Structure
title_short	Mouse Gut Microbiome-Encoded β-Glucuronidases Identified Using Metagenome Analysis Guided by Protein Structure
title_full	Mouse Gut Microbiome-Encoded β-Glucuronidases Identified Using Metagenome Analysis Guided by Protein Structure
title_fullStr	Mouse Gut Microbiome-Encoded β-Glucuronidases Identified Using Metagenome Analysis Guided by Protein Structure
title_full_unstemmed	Mouse Gut Microbiome-Encoded β-Glucuronidases Identified Using Metagenome Analysis Guided by Protein Structure
title_sort	mouse gut microbiome-encoded β-glucuronidases identified using metagenome analysis guided by protein structure
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/b1c52767175148238815600a394ac356
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Mouse Gut Microbiome-Encoded β-Glucuronidases Identified Using Metagenome Analysis Guided by Protein Structure

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