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Full-Text Articles in Medicine and Health Sciences
Motility And Adhesion Through Type Iv Pili In Gram-Positive Bacteria, Kurt H. Piepenbrink, Eric J. Sundberg
Motility And Adhesion Through Type Iv Pili In Gram-Positive Bacteria, Kurt H. Piepenbrink, Eric J. Sundberg
Food for Health: Publications
Type IV pili are hair-like bacterial surface appendages that play a role in diverse processes such as cellular adhesion, colonization, twitching motility, biofilm formation, and horizontal gene transfer. These extracellular fibers are composed exclusively or primarily of many copies of one or more pilin proteins, tightly packed in a helix so that the highly hydrophobic amino-terminus of the pilin is buried in the pilus core. Type IV pili have been characterized extensively in Gram-negative bacteria, and recent advances in high-throughput genomic sequencing have revealed that they are also widespread in Gram-positive bacteria. Here, we review the current state of knowledge …
A Generalized Framework For Computational Design And Mutational Scanning Of T-Cell Receptor Binding Interfaces, Timothy P. Riley, Cory M. Ayres, Lance M. Hellman, Nishant K. Singh, Michael Cosiano, Jennifer M. Cimons, Michael J. Anderson, Kurt H. Piepenbrink, Brian G. Pierce, Zhiping Weng, Brian M. Baker
A Generalized Framework For Computational Design And Mutational Scanning Of T-Cell Receptor Binding Interfaces, Timothy P. Riley, Cory M. Ayres, Lance M. Hellman, Nishant K. Singh, Michael Cosiano, Jennifer M. Cimons, Michael J. Anderson, Kurt H. Piepenbrink, Brian G. Pierce, Zhiping Weng, Brian M. Baker
Food for Health: Publications
T-cell receptors (TCRs) have emerged as a new class of therapeutics, most prominently for cancer where they are the key components of new cellular therapies as well as soluble biologics. Many studies have generated high affinity TCRs in order to enhance sensitivity. Recent outcomes, however, have suggested that fine manipulation of TCR binding, with an emphasis on specificity may be more valuable than large affinity increments. Structure-guided design is ideally suited for this role, and here we studied the generality of structure-guided design as applied to TCRs. We found that a previous approach, which successfully optimized the binding of a …
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 …