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Alan Cartmell - One of the best experts on this subject based on the ideXlab platform.
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Metabolism of multiple glycosaminoglycans by Bacteroides Thetaiotaomicron is orchestrated by a versatile core genetic locus
Nature Communications, 2020Co-Authors: Didier Ndeh, Arnaud Baslé, Henrik Strahl, Urszula L. Mcclurgg, Bernard Henrissat, Nicolas Terrapon, Alan CartmellAbstract:Glycosaminoglycans (GAGs) are an important nutrient source for the gut microbiome. Here, the authors characterize the genetic loci that underpins glycosaminoglycan utilization in Bacteroides Thetaiotaomicron; providing insights into the metabolism of GAGs by a predominant member of the gut microbiota. The human gut microbiota (HGM), which is critical to human health, utilises complex glycans as its major carbon source. Glycosaminoglycans represent an important, high priority, nutrient source for the HGM. Pathways for the metabolism of various glycosaminoglycan substrates remain ill-defined. Here we perform a biochemical, genetic and structural dissection of the genetic loci that orchestrates glycosaminoglycan metabolism in the organism Bacteroides Thetaiotaomicron. Here, we report: the discovery of two previously unknown surface glycan binding proteins which facilitate glycosaminoglycan import into the periplasm; distinct kinetic and genetic specificities of various periplasmic lyases which dictate glycosaminoglycan metabolic pathways; understanding of endo sulfatase activity questioning the paradigm of how the 'sulfation problem' is handled by the HGM; and 3D crystal structures of the polysaccharide utilisation loci encoded sulfatases. Together with comparative genomic studies, our study fills major gaps in our knowledge of glycosaminoglycan metabolism by the HGM.
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Metabolism of multiple glycosaminoglycans by Bacteroides Thetaiotaomicron is orchestrated by a versatile core genetic locus.
Nature Communications, 2020Co-Authors: Didier Ndeh, Arnaud Baslé, Henrik Strahl, Edwin A. Yates, Urszula L. Mcclurgg, Bernard Henrissat, Nicolas Terrapon, Alan CartmellAbstract:The human gut microbiota (HGM), which is critical to human health, utilises complex glycans as its major carbon source. Glycosaminoglycans represent an important, high priority, nutrient source for the HGM. Pathways for the metabolism of various glycosaminoglycan substrates remain ill-defined. Here we perform a biochemical, genetic and structural dissection of the genetic loci that orchestrates glycosaminoglycan metabolism in the organism Bacteroides Thetaiotaomicron. Here, we report: the discovery of two previously unknown surface glycan binding proteins which facilitate glycosaminoglycan import into the periplasm; distinct kinetic and genetic specificities of various periplasmic lyases which dictate glycosaminoglycan metabolic pathways; understanding of endo sulfatase activity questioning the paradigm of how the ‘sulfation problem’ is handled by the HGM; and 3D crystal structures of the polysaccharide utilisation loci encoded sulfatases. Together with comparative genomic studies, our study fills major gaps in our knowledge of glycosaminoglycan metabolism by the HGM.
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A surface endogalactanase in Bacteroides Thetaiotaomicron confers keystone status for arabinogalactan degradation.
Nature Microbiology, 2018Co-Authors: Alan Cartmell, Didier Ndeh, Arnaud Baslé, Nicolas Terrapon, J. Munoz-munoz, Jonathon A. Briggs, Elisabeth C. Lowe, Katherine Stott, Tiaan Heunis, Joe GrayAbstract:Glycans are major nutrients for the human gut microbiota (HGM). Arabinogalactan proteins (AGPs) comprise a heterogenous group of plant glycans in which a β1,3-galactan backbone and β1,6-galactan side chains are conserved. Diversity is provided by the variable nature of the sugars that decorate the galactans. The mechanisms by which nutritionally relevant AGPs are degraded in the HGM are poorly understood. Here we explore how the HGM organism Bacteroides Thetaiotaomicron metabolizes AGPs. We propose a sequential degradative model in which exo-acting glycoside hydrolase (GH) family 43 β1,3-galactanases release the side chains. These oligosaccharide side chains are depolymerized by the synergistic action of exo-acting enzymes in which catalytic interactions are dependent on whether degradation is initiated by a lyase or GH. We identified two GHs that establish two previously undiscovered GH families. The crystal structures of the exo-β1,3-galactanases identified a key specificity determinant and departure from the canonical catalytic apparatus of GH43 enzymes. Growth studies of Bacteroidetes spp. on complex AGP revealed 3 keystone organisms that facilitated utilization of the glycan by 17 recipient bacteria, which included B. Thetaiotaomicron. A surface endo-β1,3-galactanase, when engineered into B. Thetaiotaomicron, enabled the bacterium to utilize complex AGPs and act as a keystone organism.
Eric C Martens - One of the best experts on this subject based on the ideXlab platform.
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Bacteroides Thetaiotaomicron-infecting bacteriophage isolates inform sequence-based host range prediction
2020Co-Authors: Andrew J. Hryckowian, Nathan T Porter, Eric C Martens, Bryan D. Merrill, Will Van Treuren, Eric J. Nelson, Rebecca A. Garlena, Daniel A. Russell, Justin L. SonnenburgAbstract:Summary Our emerging view of the gut microbiome largely focuses on bacteria and less is known about other microbial components such as of bacteriophages (phages). Though phages are abundant in the gut, very few phages have been isolated from this ecosystem. Here, we report the genomes of 27 phages from the United States and Bangladesh that infect the prevalent human gut bacterium Bacteroides Thetaiotaomicron. These phages are mostly distinct from previously sequenced phages with the exception of two, which are crAss-like phages. We compare these isolates to existing human gut metagenomes, revealing similarities to previously inferred phages and additional unexplored phage diversity. Finally, we use host tropisms of these phages to identify alleles of phage structural genes associated with infectivity. This work provides a detailed view of the gut’s “viral dark matter” and a framework for future efforts to further integrate isolation- and sequencing-focused efforts to understand gut-resident phages.
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Bacteroides Thetaiotaomicron-Infecting Bacteriophage Isolates Inform Sequence-Based Host Range Predictions.
Cell Host & Microbe, 2020Co-Authors: Andrew J. Hryckowian, Nathan T Porter, Eric C Martens, Bryan D. Merrill, Will Van Treuren, Eric J. Nelson, Rebecca A. Garlena, Daniel A. Russell, Justin L. SonnenburgAbstract:Our emerging view of the gut microbiome largely focuses on bacteria, while less is known about other microbial components, such as bacteriophages (phages). Though phages are abundant in the gut, very few phages have been isolated from this ecosystem. Here, we report the genomes of 27 phages from the United States and Bangladesh that infect the prevalent human gut bacterium Bacteroides Thetaiotaomicron. These phages are mostly distinct from previously sequenced phages with the exception of two, which are crAss-like phages. We compare these isolates to existing human gut metagenomes, revealing similarities to previously inferred phages and additional unexplored phage diversity. Finally, we use host tropisms of these phages to identify alleles of phage structural genes associated with infectivity. This work provides a detailed view of the gut's "viral dark matter" and a framework for future efforts to further integrate isolation- and sequencing-focused efforts to understand gut-resident phages.
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Bacteroides Thetaiotaomicron.
Trends in Microbiology, 2018Co-Authors: Nathan T Porter, Ana S Luis, Eric C MartensAbstract:This infographic on Bacteroides Thetaiotaomicron (Bt) explores the ability of this microbe to digest a broad array of complex carbohydrates, alter its surface features, and its emerging role in gastrointestinal diseases. The infographic of Bacteroides Thetaiotaomicron (Bt) illustrates two key facets of its symbiotic lifestyle in the human gut: a broad ability to digest dietary fiber polysaccharides and host glycans, and a dynamic cell-surface architecture that promotes both interactions with and evasion of the host immune system. The starch-utilization system (Sus) is a cell-surface and periplasmic system involved in starch cleavage and transport. Over 80 additional Sus-like systems utilize substrates ranging from host glycans to plant cell wall pectins. Bt has evolved intricate strategies to interact with other microbes or its host, including modification of its surface. Some nutrient utilization pathways select for or directly trigger changes in capsular polysaccharide (CPS) expression. Like other fermentative members of the gut microbiome, Bt produces host absorbable short-chain and organic acids, which can all be absorbed by the host as a source of energy.
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differential metabolism of exopolysaccharides from probiotic lactobacilli by the human gut symbiont Bacteroides Thetaiotaomicron
Applied and Environmental Microbiology, 2015Co-Authors: Alicia Lammerts Van Bueren, Eric C Martens, Aakanksha Saraf, Lubbert DijkhuizenAbstract:Probiotic microorganisms are ingested as food or supplements and impart positive health benefits to consumers. Previous studies have indicated that probiotics transiently reside in the gastrointestinal tract and, in addition to modulating commensal species diversity, increase the expression of genes for carbohydrate metabolism in resident commensal bacterial species. In this study, it is demonstrated that the human gut commensal species Bacteroides Thetaiotaomicron efficiently metabolizes fructan exopolysaccharide (EPS) synthesized by probiotic Lactobacillus reuteri strain 121 while only partially degrading reuteran and isomalto/malto-polysaccharide (IMMP) α-glucan EPS polymers. B. Thetaiotaomicron metabolized these EPS molecules via the activation of enzymes and transport systems encoded by dedicated polysaccharide utilization loci specific for β-fructans and α-glucans. Reduced metabolism of reuteran and IMMP α-glucan EPS molecules may be due to reduced substrate binding by components of the starch utilization system (sus). This study reveals that microbial EPS substrates activate genes for carbohydrate metabolism in B. Thetaiotaomicron and suggests that microbially derived carbohydrates provide a carbohydrate-rich reservoir for B. Thetaiotaomicron nutrient acquisition in the gastrointestinal tract.
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Dynamic responses of Bacteroides Thetaiotaomicron during growth on glycan mixtures.
Molecular Microbiology, 2013Co-Authors: Theresa E. Rogers, Nicole M. Koropatkin, Nicholas A. Pudlo, Joshua S. K. Bell, Monica Moya Balasch, Kevin Jasker, Eric C MartensAbstract:Summary Bacteroides Thetaiotaomicron (Bt) is a human colonic symbiont that degrades many different complex carbohydrates (glycans), the identities and amounts of which are likely to change frequently and abruptly from meal-to-meal. To understand how this organism reacts to dynamic growth conditions, we challenged it with a series of different glycan mixtures and measured responses involved in glycan catabolism. Our results demonstrate that individual Bt cells can simultaneously respond to multiple glycans and that responses to new glycans are extremely rapid. The presence of alternative carbohydrates does not alter response kinetics, but reduces expression of some glycan utilization genes as well as the cell's sensitivity to glycans that are present in lower concentration. Growth in a mixture containing 12 different glycans revealed that Bt preferentially uses some before others. This metabolic hierarchy is not changed by prior exposure to lower priority glycans because re-introducing high priority substrates late in culture re-initiates repression of genes involved in degrading those with lower priority. At least some carbohydrate prioritization effects occur at the level of monosaccharide recognition. Our results provide insight into how a bacterial glycan generalist modifies its responses in dynamic glycan environments and provide essential knowledge to interpret related metabolic behaviour in vivo.
Jean-marc Ghigo - One of the best experts on this subject based on the ideXlab platform.
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Capsular Polysaccharide Cross-Regulation Modulates Bacteroides Thetaiotaomicron Biofilm Formation
mBio, 2020Co-Authors: Nathalie Béchon, Jovana Mihajlovic, Sol Vendrell-fernández, Florian Chain, Philippe Langella, Christophe Beloin, Jean-marc GhigoAbstract:ABSTRACT Bacteroides Thetaiotaomicron is one of the most abundant gut symbiont species, whose contribution to host health through its ability to degrade dietary polysaccharides and mature the immune system is under intense scrutiny. In contrast, adhesion and biofilm formation, which are potentially involved in gut colonization and microbiota structure and stability, have hardly been investigated in this intestinal bacterium. To uncover B. Thetaiotaomicron biofilm-related functions, we performed a transposon mutagenesis in the poorly biofilm-forming reference strain VPI-5482 and showed that capsule 4, one of the eight B. Thetaiotaomicron capsules, hinders biofilm formation. We then showed that the production of capsules 1, 2, 3, 5, and 6 also inhibits biofilm formation and that decreased capsulation of the population correlated with increased biofilm formation, suggesting that capsules could be masking adhesive surface structures. In contrast, we showed that capsule 8 displayed intrinsic adhesive properties. Finally, we demonstrated that BT2934, the wzx homolog of the B. Thetaiotaomicron glycosylation locus, competes with capsule production and impacts its adhesion capacity. This study therefore establishes B. Thetaiotaomicron capsule regulation as a major determinant of B. Thetaiotaomicron biofilm formation, providing new insights into how modulation of different B. Thetaiotaomicron surface structures affects in vitro biofilm formation. IMPORTANCE The human gut harbors a complex bacterial community that plays important roles in host health and disease, including nutrient acquisition, maturation of the immune system, and resistance to infections. The capacity to adhere to surfaces and form communities called biofilms is believed to be important for niche colonization and maintenance of gut bacteria. However, little is known about the adhesion capacity of most gut bacteria. In this study, we investigated biofilm formation in Bacteroides Thetaiotaomicron, one of the most abundant bacteria of the normal mammalian intestine. We identified that B. Thetaiotaomicron capsules, a group of eight surface-exposed polysaccharidic layers mediating important interactions with the gut environment, are also major determinants of biofilm formation that mask or unmask adhesion factors. Studying how B. Thetaiotaomicron regulates its adhesion properties will allow us to better understand the physiology and specific properties of this important gut symbiont within anaerobic biofilms.
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A Putative Type V Pilus Contributes to Bacteroides Thetaiotaomicron Biofilm Formation Capacity
Journal of Bacteriology, 2019Co-Authors: Jovana Mihajlovic, Nathalie Béchon, Florian Chain, Philippe Langella, Christophe Beloin, Christa Ivanova, Alexandre Almeida, Jean-marc GhigoAbstract:Bacteroides Thetaiotaomicron is a prominent anaerobic member of the healthy human gut microbiota. While the majority of functional studies on B. Thetaiotaomicron addressed its impact on the immune system and the utilization of diet polysaccharides, B. Thetaiotaomicron biofilm capacity and its contribution to intestinal colonization are still poorly characterized. We tested the natural adhesion of 34 B. Thetaiotaomicron isolates and showed that although biofilm capacity is widespread among B. Thetaiotaomicron strains, this phenotype is masked or repressed in the widely used reference strain VPI 5482. Using transposon mutagenesis followed by a biofilm positive-selection procedure, we identified VPI 5482 mutants with increased biofilm capacity corresponding to an alteration in the C-terminal region of BT3147, encoded by the BT3148-BT3147 locus, which displays homology with Mfa-like type V pili found in many Bacteroidetes We show that BT3147 is exposed on the B. Thetaiotaomicron surface and that BT3147-dependent adhesion also requires BT3148, suggesting that BT3148 and BT3147 correspond to the anchor and stalk subunits of a new type V pilus involved in B. Thetaiotaomicron adhesion. This study therefore introduces B. Thetaiotaomicron as a model to study proteinaceous adhesins and biofilm-related phenotypes in this important intestinal symbiont.IMPORTANCE Although the gut anaerobe Bacteroides Thetaiotaomicron is a prominent member of the healthy human gut microbiota, little is known about its capacity to adhere to surfaces and form biofilms. Here, we identify that alteration of a surface-exposed protein corresponding to a type of pili found in many Bacteroidetes increases B. Thetaiotaomicron biofilm formation. This study lays the ground for establishing this bacterium as a model organism for in vitro and in vivo studies of biofilm-related phenotypes in gut anaerobes.
Didier Ndeh - One of the best experts on this subject based on the ideXlab platform.
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Metabolism of multiple glycosaminoglycans by Bacteroides Thetaiotaomicron is orchestrated by a versatile core genetic locus
Nature Communications, 2020Co-Authors: Didier Ndeh, Arnaud Baslé, Henrik Strahl, Urszula L. Mcclurgg, Bernard Henrissat, Nicolas Terrapon, Alan CartmellAbstract:Glycosaminoglycans (GAGs) are an important nutrient source for the gut microbiome. Here, the authors characterize the genetic loci that underpins glycosaminoglycan utilization in Bacteroides Thetaiotaomicron; providing insights into the metabolism of GAGs by a predominant member of the gut microbiota. The human gut microbiota (HGM), which is critical to human health, utilises complex glycans as its major carbon source. Glycosaminoglycans represent an important, high priority, nutrient source for the HGM. Pathways for the metabolism of various glycosaminoglycan substrates remain ill-defined. Here we perform a biochemical, genetic and structural dissection of the genetic loci that orchestrates glycosaminoglycan metabolism in the organism Bacteroides Thetaiotaomicron. Here, we report: the discovery of two previously unknown surface glycan binding proteins which facilitate glycosaminoglycan import into the periplasm; distinct kinetic and genetic specificities of various periplasmic lyases which dictate glycosaminoglycan metabolic pathways; understanding of endo sulfatase activity questioning the paradigm of how the 'sulfation problem' is handled by the HGM; and 3D crystal structures of the polysaccharide utilisation loci encoded sulfatases. Together with comparative genomic studies, our study fills major gaps in our knowledge of glycosaminoglycan metabolism by the HGM.
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Metabolism of multiple glycosaminoglycans by Bacteroides Thetaiotaomicron is orchestrated by a versatile core genetic locus.
Nature Communications, 2020Co-Authors: Didier Ndeh, Arnaud Baslé, Henrik Strahl, Edwin A. Yates, Urszula L. Mcclurgg, Bernard Henrissat, Nicolas Terrapon, Alan CartmellAbstract:The human gut microbiota (HGM), which is critical to human health, utilises complex glycans as its major carbon source. Glycosaminoglycans represent an important, high priority, nutrient source for the HGM. Pathways for the metabolism of various glycosaminoglycan substrates remain ill-defined. Here we perform a biochemical, genetic and structural dissection of the genetic loci that orchestrates glycosaminoglycan metabolism in the organism Bacteroides Thetaiotaomicron. Here, we report: the discovery of two previously unknown surface glycan binding proteins which facilitate glycosaminoglycan import into the periplasm; distinct kinetic and genetic specificities of various periplasmic lyases which dictate glycosaminoglycan metabolic pathways; understanding of endo sulfatase activity questioning the paradigm of how the ‘sulfation problem’ is handled by the HGM; and 3D crystal structures of the polysaccharide utilisation loci encoded sulfatases. Together with comparative genomic studies, our study fills major gaps in our knowledge of glycosaminoglycan metabolism by the HGM.
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A surface endogalactanase in Bacteroides Thetaiotaomicron confers keystone status for arabinogalactan degradation.
Nature Microbiology, 2018Co-Authors: Alan Cartmell, Didier Ndeh, Arnaud Baslé, Nicolas Terrapon, J. Munoz-munoz, Jonathon A. Briggs, Elisabeth C. Lowe, Katherine Stott, Tiaan Heunis, Joe GrayAbstract:Glycans are major nutrients for the human gut microbiota (HGM). Arabinogalactan proteins (AGPs) comprise a heterogenous group of plant glycans in which a β1,3-galactan backbone and β1,6-galactan side chains are conserved. Diversity is provided by the variable nature of the sugars that decorate the galactans. The mechanisms by which nutritionally relevant AGPs are degraded in the HGM are poorly understood. Here we explore how the HGM organism Bacteroides Thetaiotaomicron metabolizes AGPs. We propose a sequential degradative model in which exo-acting glycoside hydrolase (GH) family 43 β1,3-galactanases release the side chains. These oligosaccharide side chains are depolymerized by the synergistic action of exo-acting enzymes in which catalytic interactions are dependent on whether degradation is initiated by a lyase or GH. We identified two GHs that establish two previously undiscovered GH families. The crystal structures of the exo-β1,3-galactanases identified a key specificity determinant and departure from the canonical catalytic apparatus of GH43 enzymes. Growth studies of Bacteroidetes spp. on complex AGP revealed 3 keystone organisms that facilitated utilization of the glycan by 17 recipient bacteria, which included B. Thetaiotaomicron. A surface endo-β1,3-galactanase, when engineered into B. Thetaiotaomicron, enabled the bacterium to utilize complex AGPs and act as a keystone organism.
Nathan T Porter - One of the best experts on this subject based on the ideXlab platform.
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Phase-variable capsular polysaccharides and lipoproteins modify bacteriophage susceptibility in Bacteroides Thetaiotaomicron.
Nature Microbiology, 2020Co-Authors: Nathan T Porter, Andrew J. Hryckowian, Bryan D. Merrill, Jaime J. Fuentes, Jackson O. Gardner, Robert W. P. Glowacki, Shaleni Singh, Ryan D. Crawford, Evan S. Snitkin, Justin L. SonnenburgAbstract:A variety of cell surface structures dictate interactions between bacteria and their environment, including their viruses (bacteriophages). Members of the human gut Bacteroidetes characteristically produce several phase-variable capsular polysaccharides (CPSs), but their contributions to bacteriophage interactions are unknown. To begin to understand how CPSs have an impact on Bacteroides–phage interactions, we isolated 71 Bacteroides Thetaiotaomicron-infecting bacteriophages from two locations in the United States. Using B. Thetaiotaomicron strains that express defined subsets of CPSs, we show that CPSs dictate host tropism for these phages and that expression of non-permissive CPS variants is selected under phage predation, enabling survival. In the absence of CPSs, B. Thetaiotaomicron escapes bacteriophage predation by altering expression of eight distinct phase-variable lipoproteins. When constitutively expressed, one of these lipoproteins promotes resistance to multiple bacteriophages. Our results reveal important roles for Bacteroides CPSs and other cell surface structures that allow these bacteria to persist under bacteriophage predation, and hold important implications for using bacteriophages therapeutically to target gut symbionts. Isolation of phages associated with the gut commensal Bacteroides Thetaiotaomicron reveals a link between cell surface structures, including phase-variable capsular polysaccharides, lipoproteins and S-layer proteins, and susceptibility to phage infection.
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Bacteroides Thetaiotaomicron-infecting bacteriophage isolates inform sequence-based host range prediction
2020Co-Authors: Andrew J. Hryckowian, Nathan T Porter, Eric C Martens, Bryan D. Merrill, Will Van Treuren, Eric J. Nelson, Rebecca A. Garlena, Daniel A. Russell, Justin L. SonnenburgAbstract:Summary Our emerging view of the gut microbiome largely focuses on bacteria and less is known about other microbial components such as of bacteriophages (phages). Though phages are abundant in the gut, very few phages have been isolated from this ecosystem. Here, we report the genomes of 27 phages from the United States and Bangladesh that infect the prevalent human gut bacterium Bacteroides Thetaiotaomicron. These phages are mostly distinct from previously sequenced phages with the exception of two, which are crAss-like phages. We compare these isolates to existing human gut metagenomes, revealing similarities to previously inferred phages and additional unexplored phage diversity. Finally, we use host tropisms of these phages to identify alleles of phage structural genes associated with infectivity. This work provides a detailed view of the gut’s “viral dark matter” and a framework for future efforts to further integrate isolation- and sequencing-focused efforts to understand gut-resident phages.
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Bacteroides Thetaiotaomicron-Infecting Bacteriophage Isolates Inform Sequence-Based Host Range Predictions.
Cell Host & Microbe, 2020Co-Authors: Andrew J. Hryckowian, Nathan T Porter, Eric C Martens, Bryan D. Merrill, Will Van Treuren, Eric J. Nelson, Rebecca A. Garlena, Daniel A. Russell, Justin L. SonnenburgAbstract:Our emerging view of the gut microbiome largely focuses on bacteria, while less is known about other microbial components, such as bacteriophages (phages). Though phages are abundant in the gut, very few phages have been isolated from this ecosystem. Here, we report the genomes of 27 phages from the United States and Bangladesh that infect the prevalent human gut bacterium Bacteroides Thetaiotaomicron. These phages are mostly distinct from previously sequenced phages with the exception of two, which are crAss-like phages. We compare these isolates to existing human gut metagenomes, revealing similarities to previously inferred phages and additional unexplored phage diversity. Finally, we use host tropisms of these phages to identify alleles of phage structural genes associated with infectivity. This work provides a detailed view of the gut's "viral dark matter" and a framework for future efforts to further integrate isolation- and sequencing-focused efforts to understand gut-resident phages.
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Bacteroides Thetaiotaomicron.
Trends in Microbiology, 2018Co-Authors: Nathan T Porter, Ana S Luis, Eric C MartensAbstract:This infographic on Bacteroides Thetaiotaomicron (Bt) explores the ability of this microbe to digest a broad array of complex carbohydrates, alter its surface features, and its emerging role in gastrointestinal diseases. The infographic of Bacteroides Thetaiotaomicron (Bt) illustrates two key facets of its symbiotic lifestyle in the human gut: a broad ability to digest dietary fiber polysaccharides and host glycans, and a dynamic cell-surface architecture that promotes both interactions with and evasion of the host immune system. The starch-utilization system (Sus) is a cell-surface and periplasmic system involved in starch cleavage and transport. Over 80 additional Sus-like systems utilize substrates ranging from host glycans to plant cell wall pectins. Bt has evolved intricate strategies to interact with other microbes or its host, including modification of its surface. Some nutrient utilization pathways select for or directly trigger changes in capsular polysaccharide (CPS) expression. Like other fermentative members of the gut microbiome, Bt produces host absorbable short-chain and organic acids, which can all be absorbed by the host as a source of energy.
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colitogenic Bacteroides Thetaiotaomicron antigens access host immune cells in a sulfatase dependent manner via outer membrane vesicles
Cell Host & Microbe, 2015Co-Authors: Christina A Hickey, Nathan T Porter, Elizabeth A. Cameron, Kristine A Kuhn, David L Donermeyer, Chunsheng Jin, Haerin Jung, Gerard E Kaiko, Marta Wegorzewska, Nicole P MalvinAbstract:Summary Microbes interact with the host immune system via several potential mechanisms. One essential step for each mechanism is the method by which intestinal microbes or their antigens access specific host immune cells. Using genetically susceptible mice ( dnKO ) that develop spontaneous, fulminant colitis, triggered by Bacteroides Thetaiotaomicron ( B. theta ), we investigated the mechanism of intestinal microbial access under conditions that stimulate colonic inflammation. B. theta antigens localized to host immune cells through outer membrane vesicles (OMVs) that harbor bacterial sulfatase activity. We deleted the anaerobic sulfatase maturating enzyme (anSME) from B. theta , which is required for post-translational activation of all B. theta sulfatase enzymes. This bacterial mutant strain did not stimulate colitis in dnKO mice. Lastly, access of B. theta OMVs to host immune cells was sulfatase dependent. These data demonstrate that bacterial OMVs and associated enzymes promote inflammatory immune stimulation in genetically susceptible hosts.
