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Articles 1 - 12 of 12
Full-Text Articles in Medical Sciences
A Novel Inhibitory Mechanism Of Mitochondrion-Dependent Apoptosis By A Herpesviral Protein, Pinghui Feng, Chengyu Liang, Young C. Shin, Xiaofei E, Weijun Zhang, Robyn Gravel, Ting-Ting Wu, Ren Sun, Edward Usherwood, Jae U. Jung
A Novel Inhibitory Mechanism Of Mitochondrion-Dependent Apoptosis By A Herpesviral Protein, Pinghui Feng, Chengyu Liang, Young C. Shin, Xiaofei E, Weijun Zhang, Robyn Gravel, Ting-Ting Wu, Ren Sun, Edward Usherwood, Jae U. Jung
Dartmouth Scholarship
Upon viral infection, cells undergo apoptosis as a defense against viral replication. Viruses, in turn, have evolved elaborate mechanisms to subvert apoptotic processes. Here, we report that a novel viral mitochondrial anti-apoptotic protein (vMAP) of murine gamma-herpesvirus 68 (gammaHV-68) interacts with Bcl-2 and voltage-dependent anion channel 1 (VDAC1) in a genetically separable manner. The N-terminal region of vMAP interacted with Bcl-2, and this interaction markedly increased not only Bcl-2 recruitment to mitochondria but also its avidity for BH3-only pro-apoptotic proteins, thereby suppressing Bax mitochondrial translocation and activation. In addition, the central and C-terminal hydrophobic regions of vMAP interacted with VDAC1. …
Characterization Of Mazfsa, An Endoribonuclease From Staphylococcus Aureus, Zhibiao Fu, Niles P. Donegan, Guido Memmi, Ambrose L. Cheung
Characterization Of Mazfsa, An Endoribonuclease From Staphylococcus Aureus, Zhibiao Fu, Niles P. Donegan, Guido Memmi, Ambrose L. Cheung
Dartmouth Scholarship
The mazEF homologs of Staphylococcus aureus, designated mazEF(sa), have been shown to cotranscribe with the sigB operon under stress conditions. In this study, we showed that MazEF(Sa), as with their Escherichia coli counterparts, compose a toxin-antitoxin module wherein MazF(Sa) leads to rapid cell growth arrest and loss in viable CFU upon overexpression. MazF(Sa) is a novel sequence-specific endoribonuclease which cleaves mRNA to inhibit protein synthesis. Using ctpA mRNA as the model substrate both in vitro and in vivo, we demonstrated that MazF(Sa) cleaves single-strand RNA preferentially at the 5' side of the first U or 3' side of the second …
All-Trans Retinoic Acid Mediates Enhanced T Reg Cell Growth, Differentiation, And Gut Homing In The Face Of High Levels Of Co-Stimulation, Micah J. Benson, Karina Pino-Lagos, Mario Rosemblatt, Randolph J. Noelle
All-Trans Retinoic Acid Mediates Enhanced T Reg Cell Growth, Differentiation, And Gut Homing In The Face Of High Levels Of Co-Stimulation, Micah J. Benson, Karina Pino-Lagos, Mario Rosemblatt, Randolph J. Noelle
Dartmouth Scholarship
We demonstrate that all-trans retinoic acid (RA) induces FoxP3(+) adaptive T regulatory cells (A-Tregs) to acquire a gut-homing phenotype (alpha 4 beta 7(+) CC chemokine receptor 9(+)) and the capacity to home to the lamina propria of the small intestine. Under conditions that favor the differentiation of A-Tregs (transforming growth factor-beta1 and interleukin 2) in vitro, the inclusion of RA induces nearly all activated CD4(+) T cells to express FoxP3 and greatly increases the accumulation of these cells. In the absence of RA, A-Treg differentiation is abruptly impaired by proficient antigen presenting cells or through direct co-stimulation. In the presence …
A Serratia Marcescens Oxyr Homolog Mediates Surface Attachment And Biofilm Formation, Robert M. Q. Shanks, Nicholas A. Stella, Eric J. Kalivoda, Megan R. Doe
A Serratia Marcescens Oxyr Homolog Mediates Surface Attachment And Biofilm Formation, Robert M. Q. Shanks, Nicholas A. Stella, Eric J. Kalivoda, Megan R. Doe
Dartmouth Scholarship
OxyR is a conserved bacterial transcription factor with a regulatory role in oxidative stress response. From a genetic screen for genes that modulate biofilm formation in the opportunistic pathogen Serratia marcescens, mutations in an oxyR homolog and predicted fimbria structural genes were identified. S. marcescens oxyR mutants were severely impaired in biofilm formation, in contrast to the hyperbiofilm phenotype exhibited by oxyR mutants of Escherichia coli and Burkholderia pseudomallei. Further analysis revealed that OxyR plays a role in the primary attachment of cells to a surface. Similar to what is observed in other bacterial species, S. marcescens OxyR …
Molecular Basis Of Resistance To Muramidase And Cationic Antimicrobial Peptide Activity Of Lysozyme In Staphylococci, Silvia Herbert, Agnieszka Bera, Christiane Nerz, Dirk Kraus, Andreas Peschel, Christiane Goerke, Michael Meehl, Ambrose Cheung, Friedrich Gotz
Molecular Basis Of Resistance To Muramidase And Cationic Antimicrobial Peptide Activity Of Lysozyme In Staphylococci, Silvia Herbert, Agnieszka Bera, Christiane Nerz, Dirk Kraus, Andreas Peschel, Christiane Goerke, Michael Meehl, Ambrose Cheung, Friedrich Gotz
Dartmouth Scholarship
It has been shown recently that modification of peptidoglycan by O-acetylation renders pathogenic staphylococci resistant to the muramidase activity of lysozyme. Here, we show that a Staphylococcus aureus double mutant defective in O-acetyltransferase A (OatA), and the glycopeptide resistance-associated two-component system, GraRS, is much more sensitive to lysozyme than S. aureus with the oatA mutation alone. The graRS single mutant was resistant to the muramidase activity of lysozyme, but was sensitive to cationic antimicrobial peptides (CAMPs) such as the human lysozyme-derived peptide 107R-A-W-V-A-W-R-N-R115 (LP9), polymyxin B, or gallidermin. A comparative transcriptome analysis of wild …
Phenotypic Alterations In Type Ii Alveolar Epithelial Cells In Cd4+ T Cell Mediated Lung Inflammation, Marcus Gereke, Lothar Gröbe, Silvia Prettin, Michael Kasper, Stefanie Deppenmeier, Achim D. Gruber, Richard I. Enelow, Jan Buer, Dunja Bruder
Phenotypic Alterations In Type Ii Alveolar Epithelial Cells In Cd4+ T Cell Mediated Lung Inflammation, Marcus Gereke, Lothar Gröbe, Silvia Prettin, Michael Kasper, Stefanie Deppenmeier, Achim D. Gruber, Richard I. Enelow, Jan Buer, Dunja Bruder
Dartmouth Scholarship
Although the contribution of alveolar type II epithelial cell (AEC II) activities in various aspects of respiratory immune regulation has become increasingly appreciated, our understanding of the contribution of AEC II transcriptosome in immunopathologic lung injury remains poorly understood. We have previously established a mouse model for chronic T cell-mediated pulmonary inflammation in which influenza hemagglutinin (HA) is expressed as a transgene in AEC II, in mice expressing a transgenic T cell receptor specific for a class II-restricted epitope of HA. Pulmonary inflammation in these mice occurs as a result of CD4+ T cell recognition of alveolar antigen. This model …
The Flagellum Of Pseudomonas Aeruginosa Is Required For Resistance To Clearance By Surfactant Protein A, Shiping Zhang, Francis X. Mccormack, Roger C. Levesque, George A. O'Toole, Gee W. Lau
The Flagellum Of Pseudomonas Aeruginosa Is Required For Resistance To Clearance By Surfactant Protein A, Shiping Zhang, Francis X. Mccormack, Roger C. Levesque, George A. O'Toole, Gee W. Lau
Dartmouth Scholarship
Surfactant protein A (SP-A) is an important lung innate immune protein that kills microbial pathogens by opsonization and membrane permeabilization. We investigated the basis of SP-A-mediated pulmonary clearance of Pseudomonas aeruginosa using genetically-engineered SP-A mice and a library of signature-tagged P. aeruginosa mutants. A mutant with an insertion into flgE, the gene that encodes flagellar hook protein, was preferentially cleared by the SP-A(+/+) mice, but survived in the SP-A(-/-) mice. Opsonization by SP-A did not play a role in flgE clearance. However, exposure to SP-A directly permeabilized and killed the flgE mutant, but not the wild-type parental strain. P. aeruginosa …
Crystal Structure Of The Vibrio Cholerae Quorum-Sensing Regulatory Protein Hapr, Rukman S. De Silva, Gabriela Kovacikova, Wei Lin, Ronald K. Taylor, Karen Skorupski, F. Jon Kull
Crystal Structure Of The Vibrio Cholerae Quorum-Sensing Regulatory Protein Hapr, Rukman S. De Silva, Gabriela Kovacikova, Wei Lin, Ronald K. Taylor, Karen Skorupski, F. Jon Kull
Dartmouth Scholarship
Quorum sensing in Vibrio cholerae involves signaling between two-component sensor protein kinases and the response regulator LuxO to control the expression of the master regulator HapR. HapR, in turn, plays a central role in regulating a number of important processes, such as virulence gene expression and biofilm formation. We have determined the crystal structure of HapR to 2.2-Å resolution. Its structure reveals a dimeric, two-domain molecule with an all-helical structure that is strongly conserved with members of the TetR family of transcriptional regulators. The N-terminal DNA-binding domain contains a helix-turn-helix DNA-binding motif and alteration of certain residues in this domain …
The Pseudomonas Aeruginosa Secreted Protein Pa2934 Decreases Apical Membrane Expression Of The Cystic Fibrosis Transmembrane Conductance Regulator, Daniel P. Maceachran, Siying Ye, Jennifer M. Bomberger, Deborah A. Hogan, Agnieszka Swiatecka-Urban, Bruce Stanton, George A. O'Toole
The Pseudomonas Aeruginosa Secreted Protein Pa2934 Decreases Apical Membrane Expression Of The Cystic Fibrosis Transmembrane Conductance Regulator, Daniel P. Maceachran, Siying Ye, Jennifer M. Bomberger, Deborah A. Hogan, Agnieszka Swiatecka-Urban, Bruce Stanton, George A. O'Toole
Dartmouth Scholarship
We previously reported that Pseudomonas aeruginosa PA14 secretes a protein that can reduce the apical membrane expression of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Here we report that we have used a proteomic approach to identify this secreted protein as PA2934 [corrected], and we have named the gene cif, for CFTR inhibitory factor. We demonstrate that Cif is a secreted protein and is found associated with outer membrane-derived vesicles. Expression of Cif in Escherichia coli and purification of the C-terminal six-His-tagged Cif protein showed that Cif is necessary and sufficient to mediate the reduction in apical membrane expression …
Cpg Hypomethylation In A Large Domain Encompassing The Embryonic Β-Like Globin Genes In Primitive Erythrocytes, Mei Hsu, Rodwell R. Mabaera, Christopher H. Lowrey, David I. K. Martin, Steven Fiering
Cpg Hypomethylation In A Large Domain Encompassing The Embryonic Β-Like Globin Genes In Primitive Erythrocytes, Mei Hsu, Rodwell R. Mabaera, Christopher H. Lowrey, David I. K. Martin, Steven Fiering
Dartmouth Scholarship
There is little evidence addressing the role of CpG methylation in transcriptional control of genes that do not contain CpG islands. This is reflected in the ongoing debate about whether CpG methylation merely suppresses retroelements or if it also plays a role in developmental and tissue-specific gene regulation. The genes of the β-globin locus are an important model of mammalian developmental gene regulation and do not contain CpG islands. We have analyzed the methylation status of regions in the murine β-like globin locus in uncultured primitive and definitive erythroblasts and other cultured primary and transformed cell types. A large (∼20-kb) …
Membrane Association And Multimerization Of Tcpt, The Cognate Atpase Ortholog Of The Vibrio Cholerae Toxin-Coregulated-Pilus Biogenesis Apparatus, Shital A. Tripathi, Ronald K. Taylor
Membrane Association And Multimerization Of Tcpt, The Cognate Atpase Ortholog Of The Vibrio Cholerae Toxin-Coregulated-Pilus Biogenesis Apparatus, Shital A. Tripathi, Ronald K. Taylor
Dartmouth Scholarship
The toxin-coregulated pilus (TCP) is one of the major virulence factors of Vibrio cholerae. Biogenesis of this type 4 pilus (Tfp) requires a number of structural components encoded by the tcp operon. TcpT, the cognate putative ATPase, is required for TCP biogenesis and all TCP-mediated functions. We studied the stability and localization of TcpT in cells containing in-frame deletions in each of the tcp genes. TcpT was detectable in each of the biogenesis mutants except the ΔtcpT strain. TcpT was localized to the inner membrane (IM) in a TcpR-dependent manner. TcpR is a predicted bitopic inner membrane protein …
Inverse Regulation Of Biofilm Formation And Swarming Motility By Pseudomonas Aeruginosa Pa14, Nicky C. Caiazza, Judith H. Merritt, Kimberly M. Brothers, George A. O'Toole
Inverse Regulation Of Biofilm Formation And Swarming Motility By Pseudomonas Aeruginosa Pa14, Nicky C. Caiazza, Judith H. Merritt, Kimberly M. Brothers, George A. O'Toole
Dartmouth Scholarship
We previously reported that SadB, a protein of unknown function, is required for an early step in biofilm formation by the opportunistic pathogen Pseudomonas aeruginosa. Here we report that a mutation in sadB also results in increased swarming compared to the wild-type strain. Our data are consistent with a model in which SadB inversely regulates biofilm formation and swarming motility via its ability both to modulate flagellar reversals in a viscosity-dependent fashion and to influence the production of the Pel exopolysaccharide. We also show that SadB is required to properly modulate flagellar reversal rates via chemotaxis cluster IV (CheIV cluster). …