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- Gut microbiota (4)
- DAPI staining (3)
- Electron transport rate (3)
- Flow cytometry (3)
- Mechanic chopping (3)
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- Nuclear genome size estimation (3)
- Xanthophyll cycle pigments (3)
- Zygnema circumcarinatum (3)
- Anhedonia (2)
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- Clostridium difficile (2)
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- Microbiota-gut-brain axis (2)
- Peptide-MHC (2)
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- T-cell receptor (2)
- Whole grains (2)
- Acidogenicity (1)
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- Ascomycota; phytopathogenicity; orthologous gene groups; functional annotation (1)
Articles 31 - 47 of 47
Full-Text Articles in Medical Microbiology
Structural Diversity In The Type Iv Pili Of Multidrug-Resistant Acinetobacter, Kurt H. Piepenbrink, Erik Lillehoj, Christian M. Harding, Jason W. Labonte, Xiaotong Zuo, Chelsea A. Rapp, Robert S. Munson Jr, Simeon E. Goldblum, Mario F. Feldman, Jeffrey J. Gray, Eric J. Sundberg
Structural Diversity In The Type Iv Pili Of Multidrug-Resistant Acinetobacter, Kurt H. Piepenbrink, Erik Lillehoj, Christian M. Harding, Jason W. Labonte, Xiaotong Zuo, Chelsea A. Rapp, Robert S. Munson Jr, Simeon E. Goldblum, Mario F. Feldman, Jeffrey J. Gray, Eric J. Sundberg
Food for Health: Publications
Acinetobacter baumannii is a Gram-negative coccobacillus found primarily in hospital settings that has recently emerged as a source of hospital-acquired infections. A. baumannii expresses a variety of virulence factors, including type IV pili, bacterial extracellular appendages often essential for attachment to host cells. Here, we report the high resolution structures of the major pilin subunit, PilA, from three Acinetobacter strains, demonstrating thatA. baumannii subsets produce morphologically distinct type IV pilin glycoproteins. We examine the consequences of this heterogeneity for protein folding and assembly as well as host-cell adhesion by Acinetobacter. Comparisons of genomic and structural data with pilin proteins from …
The Neu1-Selective Sialidase Inhibitor, C9- Butyl-Amide-Dana, Blocks Sialidase Activity And Neu1-Mediated Bioactivities In Human Lung In Vitro And Murine Lung In Vivo, Sang W. Hyun, Anguo Liu, Zhenguo Liu, Alan S. Cross, Avelino C. Verceles, Sadagopan Magesh, Yadagiri Kommagalla, Chandrababunaidu Kona, Hiromune Ando, Irina G. Luzina, Sergei P. Atamas, Kurt H. Piepenbrink, Eric J. Sundberg, Wei Guang, Hideharu Ishida, Erik P. Lillehoj, Simeon E. Goldblum
The Neu1-Selective Sialidase Inhibitor, C9- Butyl-Amide-Dana, Blocks Sialidase Activity And Neu1-Mediated Bioactivities In Human Lung In Vitro And Murine Lung In Vivo, Sang W. Hyun, Anguo Liu, Zhenguo Liu, Alan S. Cross, Avelino C. Verceles, Sadagopan Magesh, Yadagiri Kommagalla, Chandrababunaidu Kona, Hiromune Ando, Irina G. Luzina, Sergei P. Atamas, Kurt H. Piepenbrink, Eric J. Sundberg, Wei Guang, Hideharu Ishida, Erik P. Lillehoj, Simeon E. Goldblum
Food for Health: Publications
Neuraminidase-1 (NEU1) is the predominant sialidase expressed in human airway epithelia and lung microvascular endothelia where it mediates multiple biological processes. We tested whether the NEU1-selective sialidase inhibitor, C9-butyl-amide-2-deoxy-2,3-dehydro-Nacetylneuraminic acid (C9-BA-DANA), inhibits one or more established NEU1-mediated bioactivities in human lung cells. We established the IC50 values of C9-BA-DANA for total sialidase activity in human airway epithelia, lung microvascular endothelia and lung fibroblasts to be 3.74 µM, 13.0 µM and 4.82 µM, respectively. In human airway epithelia, C9-BA-DANA dose-dependently inhibited flagellin-induced, NEU1-mediated mucin-1 ectodomain desialylation, adhesiveness for Pseudomonas aeruginosa and shedding. In lung microvascular endothelia, C9-BA-DANA reversed NEU1-driven restraint of …
Type Iv Pili Promote Early Biofilm Formation By Clostridium Difficile, Grace A. Maldarelli, Kurt H. Piepenbrink, Alison J. Scott, Jeffrey A. Freiberg, Yang Song, Yvonee Achermann, Robert K. Ernst, Mark E. Shirtliff, Eric J. Sundberg, Michael S. Donnenberg, Erik C. Von Rosenvinge
Type Iv Pili Promote Early Biofilm Formation By Clostridium Difficile, Grace A. Maldarelli, Kurt H. Piepenbrink, Alison J. Scott, Jeffrey A. Freiberg, Yang Song, Yvonee Achermann, Robert K. Ernst, Mark E. Shirtliff, Eric J. Sundberg, Michael S. Donnenberg, Erik C. Von Rosenvinge
Food for Health: Publications
Increasing morbidity and mortality from Clostridium difficile infection (CDI) present an enormous challenge to healthcare systems. Clostridium difficile express type IV pili (T4P), but their function remains unclear. Many chronic and recurrent bacterial infections result from biofilms, surface-associated bacterial communities embedded in an extracellular matrix. CDI may be biofilm mediated; T4P are important for biofilm formation in a number of organisms. We evaluate the role of T4P in C. difficile biofilm formation using RNA sequencing, mutagenesis and complementation of the gene encoding the major pilin pilA1, and microscopy. RNA sequencing demonstrates that, in comparison to other growth phenotypes, C. difficile …
Structural And Evolutionary Analyses Show Unique Stabilization Strategies In The Type Iv Pili Of Clostridium Difficile, Kurt H. Piepenbrink, Grace A. Maldarelli, Claudia F. Martinez De La Pena, Tanis C. Dingle, George L. Mulvey, Amanda Lee, Erik Von Rosenvinge, Glen D. Armstrong, Michael S. Donnenberg, Eric J. Sundberg
Structural And Evolutionary Analyses Show Unique Stabilization Strategies In The Type Iv Pili Of Clostridium Difficile, Kurt H. Piepenbrink, Grace A. Maldarelli, Claudia F. Martinez De La Pena, Tanis C. Dingle, George L. Mulvey, Amanda Lee, Erik Von Rosenvinge, Glen D. Armstrong, Michael S. Donnenberg, Eric J. Sundberg
Food for Health: Publications
Type IV pili are produced by many pathogenic Gram-negative bacteria and are important for processes as diverse as twitching motility, biofilm formation, cellular adhesion and horizontal gene transfer. However, many Gram-positive species, including C. difficile, also produce Type IV pili. Here, we identify the major subunit of the Type IV pili of C. difficile, PilA1, and describe multiple three-dimensional structures of PilA1, demonstrating the diversity found in three strains of C. difficile. We also model the incorporation of both PilA1 and a minor pilin, PilJ, into the pilus fiber. Although PilA1 contains no cysteine residues, and therefore cannot form the …
Plasticity In The Contribution Of T Cell Receptor Variable Region Residues To Binding Of Peptide-Hla-A2 Complexes, Sheena N. Smith, Daniel Sommermeyer, Kurt H. Piepenbrink, Sydney J. Blevins, Helga Bernhard, Wolfgang Uckert, Brian M. Baker, David M. Kranz
Plasticity In The Contribution Of T Cell Receptor Variable Region Residues To Binding Of Peptide-Hla-A2 Complexes, Sheena N. Smith, Daniel Sommermeyer, Kurt H. Piepenbrink, Sydney J. Blevins, Helga Bernhard, Wolfgang Uckert, Brian M. Baker, David M. Kranz
Food for Health: Publications
One hypothesis to account for MHC-restriction by T cell receptors (TCRs) holds that there are several evolutionary-conserved residues in TCR variable regions that contact MHC. While this ‘germline-codon’ hypothesis is supported by various lines of evidence, it has been difficult to test. The difficulty stems in part from the fact that TCRs exhibit low affinities for pep/MHC, thus limiting the range of binding energies that can be assigned to these key interactions using mutational analyses. To measure the magnitude of binding energies involved, here we used high affinity TCRs engineered by mutagenesis of CDR3. The TCRs included a high-affinity, MART-1/ …
A Novel Multivalent, Single-Domain Antibody Targeting Tcda And Tcdb Prevents Fulminant Clostridium Difficile Infection In Mice, Zhiyong Yang, Diane Schmidt, Weilong Liu, Shan Li, Lianfa Shi, Jinliang Sheng, Kevin Chen, Hua Yu, Jacqueline M. Tremblay, Xinhua Chen, Kurt H. Piepenbrink, Eric J. Sundberg, Ciaran P. Kelly, Guang Bai, Charles B. Shoemaker, Hanping Feng
A Novel Multivalent, Single-Domain Antibody Targeting Tcda And Tcdb Prevents Fulminant Clostridium Difficile Infection In Mice, Zhiyong Yang, Diane Schmidt, Weilong Liu, Shan Li, Lianfa Shi, Jinliang Sheng, Kevin Chen, Hua Yu, Jacqueline M. Tremblay, Xinhua Chen, Kurt H. Piepenbrink, Eric J. Sundberg, Ciaran P. Kelly, Guang Bai, Charles B. Shoemaker, Hanping Feng
Food for Health: Publications
The incidence of Clostridium difficile infection (CDI) and associated mortality have increased rapidly worldwide in recent years. Therefore, it is critical to develop new therapies for CDI. In this study, we generated a novel, potently neutralizing, tetravalent, and bispecific antibody composed of 2 heavy-chain-only VH (VHH) binding domains against both TcdA and TcdB (designated “ABA”) that reverses fulminant CDI in mice infected with an epidemic 027 strain after a single injection of the antibody. We demonstrated that ABA bound to both toxins simultaneously and displayed a significantly enhanced neutralizing activity both in vitro and in vivo. Additionally, …
Recruitment Of Tlr Adapter Trif To Tlr4 Signaling Complex Is Mediated By The Second Helical Region Of Trif Tir Domain, Wenji Piao, Lisa W. Ru, Kurt H. Piepenbrink, Eric J. Sundberg, Stefanie N. Vogel, Vladimir Y. Toshchakov
Recruitment Of Tlr Adapter Trif To Tlr4 Signaling Complex Is Mediated By The Second Helical Region Of Trif Tir Domain, Wenji Piao, Lisa W. Ru, Kurt H. Piepenbrink, Eric J. Sundberg, Stefanie N. Vogel, Vladimir Y. Toshchakov
Food for Health: Publications
Toll/IL-1R resistance (TIR) domain–containing adapter-inducing IFN-β (TRIF) is a Toll-like receptor (TLR) adapter that mediates MyD88-independent induction of type I interferons through activation of IFN regulatory factor 3 and NFκB. We have examined peptides derived from the TRIF TIR domain for ability to inhibit TLR4. In addition to a previously identified BB loop peptide (TF4), a peptide derived from putative helix B of TRIF TIR (TF5) strongly inhibits LPS-induced cytokine and MAPK activation in wild-type cells. TF5 failed to inhibit LPS-induced cytokine and kinase activation in TRIF-deficient immortalized bone-marrow–derived macrophage, but was fully inhibitory in MyD88 knockout cells. TF5 does …
Methods For Quantifying T Cell Receptor Binding Affinities And Thermodynamics, Kurt H. Piepenbrink, Brian E. Gloor, Kathryn M. Armstrong, Brian M. Baker
Methods For Quantifying T Cell Receptor Binding Affinities And Thermodynamics, Kurt H. Piepenbrink, Brian E. Gloor, Kathryn M. Armstrong, Brian M. Baker
Food for Health: Publications
αβ T cell receptors (TCRs) recognize peptide antigens bound and presented by class I or class II major histocompatibility complex (MHC) proteins. Recognition of a peptide/MHC complex is required for initiation and propagation of a cellular immune response, as well as the development and maintenance of the T cell repertoire. Here we discuss methods to quantify the affinities and thermodynamics of interactions between soluble ectodomains of TCRs and their peptide/MHC ligands, focusing on titration calorimetry, surface plasmon resonance, and fluorescence anisotropy. As TCRs typically bind ligand with weak-to-moderate affinities, we focus the discussion on means to enhance the accuracy and …
Holobiont Nutrition: Considering The Role Of The Gastrointestinal Microbiota In The Health Benefits Of Whole Grains, Jens Walter, Ines Martinez, Devin J. Rose
Holobiont Nutrition: Considering The Role Of The Gastrointestinal Microbiota In The Health Benefits Of Whole Grains, Jens Walter, Ines Martinez, Devin J. Rose
Food for Health: Publications
Intake of whole grains and other food products high in dietary fiber have long been linked to the prevention of chronic diseases associated with inflammation. A contribution of the gastrointestinal microbiota to these effects has been suggested, but little is known on how whole grains interact with gut bacteria. We have recently published the first human trial that made use of next-generation sequencing to determine the effect of whole grains (whole grain barley, brown rice or a mixture of the two) on fecal microbiota structure and tested for associations between the gut microbiota and blood markers of inflammation, glucose and …
Gut Microbiome Composition Is Linked To Whole Grain-Induced Immunological Improvements, Ines Martinez, James M. Lattimer, Kelcie L. Hubach, Jennifer A. Case, Junyi Yang, Casey G. Weber, Julie A. Louk, Devin J. Rose, Gayaneh Kyureghian, Daniel A. Peterson, Mark D. Haub, Jens Walter
Gut Microbiome Composition Is Linked To Whole Grain-Induced Immunological Improvements, Ines Martinez, James M. Lattimer, Kelcie L. Hubach, Jennifer A. Case, Junyi Yang, Casey G. Weber, Julie A. Louk, Devin J. Rose, Gayaneh Kyureghian, Daniel A. Peterson, Mark D. Haub, Jens Walter
Food for Health: Publications
The involvement of the gut microbiota in metabolic disorders, and the ability of whole grains to affect both host metabolism and gut microbial ecology, suggest that some benefits of whole grains are mediated through their effects on the gut microbiome. Nutritional studies that assess the effect of whole grains on both the gut microbiome and human physiology are needed. We conducted a randomized cross-over trial with four-week treatments in which 28 healthy humans consumed a daily dose of 60 g of whole-grain barley (WGB), brown rice (BR), or an equal mixture of the two (BR+WGB), and characterized their impact on …
Single-Chain Vαvβ T Cell Receptors Function Without Mispairing With Endogenous Tcr Chains1, David H. Aggen, Adam S. Chervin, Thomas M. Schmitt, Boris Engels, Jennifer D. Stone, Sarah A. Richman, Kurt H. Piepenbrink, Brian M. Baker, Philip D. Greenberg, Hans Schreiber, David M. Kranz
Single-Chain Vαvβ T Cell Receptors Function Without Mispairing With Endogenous Tcr Chains1, David H. Aggen, Adam S. Chervin, Thomas M. Schmitt, Boris Engels, Jennifer D. Stone, Sarah A. Richman, Kurt H. Piepenbrink, Brian M. Baker, Philip D. Greenberg, Hans Schreiber, David M. Kranz
Food for Health: Publications
Transduction of exogenous T cell receptor (TCR) genes into patients’ activated peripheral blood T cells is a potent strategy to generate large numbers of specific T cells for adoptive therapy of cancer and viral diseases. However, the remarkable clinical promise of this powerful approach is still being overshadowed by a serious potential consequence: mispairing of the exogenous TCR chains with endogenous TCR chains. These “mixed” heterodimers can generate new specificities that result in graft-versus-host reactions. Engineering TCR constant regions of the exogenous chains with a cysteine promotes proper pairing and reduces the mispairing, but, as we show here, does not …
Conformational Melding Permits A Conserved Binding Geometry In Tcr Recognition Of Foreign And Self Molecular Mimics, Oleg Y. Borbulevych, Kurt H. Piepenbrink, Brian M. Baker
Conformational Melding Permits A Conserved Binding Geometry In Tcr Recognition Of Foreign And Self Molecular Mimics, Oleg Y. Borbulevych, Kurt H. Piepenbrink, Brian M. Baker
Food for Health: Publications
Molecular mimicry between foreign and self antigens is a mechanism of T cell receptor cross reactivity and is thought to contribute to the development of autoimmunity. The αβ TCR A6 recognizes the foreign antigen Tax from the virus HTLV-1 when presented by the class I MHC HLA-A2. In a possible link with the autoimmune disease HAM/TSP, A6 also recognizes a self peptide from the neuronal protein HuD in the context of HLA-A2. We found here that the complexes of the HuD and Tax epitopes with HLA-A2 are close but imperfect structural mimics, and that in contrast with other recent structures …
Disparate Degrees Of Hypervariable Loop Flexibility Control T Cell Receptor Cross-Reactivity, Specificity, And Binding Mechanism, Daniel R. Scott, Oleg Y. Borbulevych, Kurt H. Piepenbrink, Steven A. Corcelli, Brian M. Baker
Disparate Degrees Of Hypervariable Loop Flexibility Control T Cell Receptor Cross-Reactivity, Specificity, And Binding Mechanism, Daniel R. Scott, Oleg Y. Borbulevych, Kurt H. Piepenbrink, Steven A. Corcelli, Brian M. Baker
Food for Health: Publications
αβ T cell receptors recognize multiple antigenic peptides bound and presented by major histocompatibility complex molecules. TCR cross-reactivity has been attributed in part to flexibility of the complementarity-determining region loops, yet there have been limited direct studies of loop dynamics to determine the extent of its role. Here we studied the flexibility of the binding loops of the αβ TCR A6 utilizing crystallographic, spectroscopic, and computational methods. A significant role for flexibility in binding and cross-reactivity was indicated only for the CDR3α and CDR3β hypervariable loops. Examination of the energy landscapes of these two loops indicated that CDR3β possesses a …
Identification And Engineering Of Human Variable Regions That Allow Expression Of Stable Single-Chain T Cell Receptors, David H. Aggen, Adam S. Chervin, Francis K. Insaidoo, Kurt H. Piepenbrink, Brian M. Baker, David M. Kranz
Identification And Engineering Of Human Variable Regions That Allow Expression Of Stable Single-Chain T Cell Receptors, David H. Aggen, Adam S. Chervin, Francis K. Insaidoo, Kurt H. Piepenbrink, Brian M. Baker, David M. Kranz
Food for Health: Publications
Single-chain antibody fragments (scFv), consisting of two linked variable regions (VH and VL), are a versatile format for engineering and as potential antigen-specific therapeutics. Although the analogous format for T cell receptors (TCRs), consisting of two linked V regions (Vα and Vβ; referred to here as scTv), could provide similar opportunities, all wild-type scTv proteins examined to date are unstable. This obstacle has prevented scTv fragments from being widely used for engineering or therapeutics. To further explore whether some stable human scTv fragments could be expressed, we used a yeast system in which display of properly folded …
Fluorine Substitutions In An Antigenic Peptide Selectively Modulate T Cell Receptor Binding In A Minimally Perturbing Manner, Kurt H. Piepenbrink, Oleg Y. Borbulevych, Ruth F. Sommese, John Clemens, Kathrynq M. Armstrong, Clare Desmond, Priscilla Do, Brian M. Baker
Fluorine Substitutions In An Antigenic Peptide Selectively Modulate T Cell Receptor Binding In A Minimally Perturbing Manner, Kurt H. Piepenbrink, Oleg Y. Borbulevych, Ruth F. Sommese, John Clemens, Kathrynq M. Armstrong, Clare Desmond, Priscilla Do, Brian M. Baker
Food for Health: Publications
T cell receptor (TCR) recognition of antigenic peptides bound and presented by major histocompatibility complex (MHC) molecules forms the basis of the cellular immune response to pathogens and cancer. TCRs bind peptide/MHC molecules weakly and with fast kinetics, features which have hindered detailed biophysical studies of these interactions. Modified peptides resulting in enhanced TCR binding could help overcome these challenges. Further, there is considerable interest in using modified peptides with enhanced TCR binding as the basis for clinical vaccines. Here, we studied how fluorine substitutions in an antigenic peptide can selectively impact TCR recognition. Using a structure-guided design approach, we …
T Cell Receptor Cross-Reactivity Directed By Antigen-Dependent Tuning Of Peptide-Mhc Molecular Flexibility, Oleg Y. Borbulevych, Kurt H. Piepenbrink, Brian E. Gloor, Daniel R. Scott, Ruth F. Sommese, David K. Cole, Andrew K. Sewell, Brian M. Baker
T Cell Receptor Cross-Reactivity Directed By Antigen-Dependent Tuning Of Peptide-Mhc Molecular Flexibility, Oleg Y. Borbulevych, Kurt H. Piepenbrink, Brian E. Gloor, Daniel R. Scott, Ruth F. Sommese, David K. Cole, Andrew K. Sewell, Brian M. Baker
Food for Health: Publications
Tell mediated immunity requires T cell receptor (TCR) cross-reactivity, the mechanisms behind which remain incompletely elucidated. The αβ TCR A6 recognizes both the Tax (LLFGYPVYV) and Tel1p (MLWGYLQYV) peptides presented by the human class I MHC molecule HLA-A2. Here we found that although the two ligands are ideal structural mimics, they form substantially different interfaces with A6, with conformational differences in the peptide, the TCR, and unexpectedly, the MHC molecule. The differences between the Tax and Tel1p ternary complexes could not be predicted from the free peptide-MHC structures and are inconsistent with a traditional induced-fit mechanism. Instead, the differences were …
Conformational Changes And Flexibility In T-Cell Receptor Recognition Of Peptide–Mhc Complexes, Kathryn M. Armstrong, Kurt H. Piepenbrink, Brian M. Baker
Conformational Changes And Flexibility In T-Cell Receptor Recognition Of Peptide–Mhc Complexes, Kathryn M. Armstrong, Kurt H. Piepenbrink, Brian M. Baker
Food for Health: Publications
A necessary feature of the immune system, TCR (T-cell receptor) cross-reactivity has been implicated in numerous autoimmune pathologies and is an underlying cause of transplant rejection. Early studies of the interactions of αβ TCRs (T-cell receptors) with their peptide–MHC ligands suggested that conformational plasticity in the TCR CDR (complementarity determining region) loops is a dominant contributor to T-cell cross-reactivity. Since these initial studies, the database of TCRs whose structures have been solved both bound and free is now large enough to permit general conclusions to be drawn about the extent of TCR plasticity and the types and locations of motion …