Journal ArticleDOI
Identification of the cellular receptor for anthrax toxin.
Kenneth A. Bradley,Jeremy Mogridge,Jeremy Mogridge,Michael Mourez,Robert J. Collier,John A. Young +5 more
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TLDR
The cloning of the human PA receptor is described using a genetic complementation approach and a soluble version of this domain can protect cells from the action of the toxin.Abstract:
The tripartite toxin secreted by Bacillus anthracis, the causative agent of anthrax, helps the bacterium evade the immune system and can kill the host during a systemic infection. Two components of the toxin enzymatically modify substrates within the cytosol of mammalian cells: oedema factor (OF) is an adenylate cyclase that impairs host defences through a variety of mechanisms including inhibiting phagocytosis; lethal factor (LF) is a zinc-dependent protease that cleaves mitogen-activated protein kinase kinase and causes lysis of macrophages. Protective antigen (PA), the third component, binds to a cellular receptor and mediates delivery of the enzymatic components to the cytosol. Here we describe the cloning of the human PA receptor using a genetic complementation approach. The receptor, termed ATR (anthrax toxin receptor), is a type I membrane protein with an extracellular von Willebrand factor A domain that binds directly to PA. In addition, a soluble version of this domain can protect cells from the action of the toxin.read more
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Transcriptome dysregulation by anthrax lethal toxin plays a key role in induction of human endothelial cell cytotoxicity
Monica Rolando,Caroline Stefani,Caroline Stefani,Gilles Flatau,Gilles Flatau,Patrick Auberger,Patrick Auberger,Amel Mettouchi,Musa M. Mhlanga,Ulf R. Rapp,Antoine Galmiche,Emmanuel Lemichez +11 more
TL;DR: DNA array analysis shows that LT has a major impact on the cell transcriptome and key host genes involved in LT cytotoxic effects are identified, and upregulation of TRAIL and downregulation of XIAP both participate in LT‐induced caspase‐3 activation.
Journal ArticleDOI
Identification of Amino Acid Residues of Anthrax Protective Antigen Involved in Binding with Lethal Factor
Vibha Chauhan,Rakesh Bhatnagar +1 more
TL;DR: It was concluded that residues 202, 203, 205, and 207 of PA are essential for the binding of LF to PA.
Journal ArticleDOI
Anthrax Edema Toxin Sensitizes DBA/2J Mice to Lethal Toxin
Aaron M. Firoved,Mahtab Moayeri,Jason F. Wiggins,Yuequan Shen,Wei-Jen Tang,Stephen H. Leppla +5 more
TL;DR: It is reported that a low dose of ET is sufficient to sensitize DBA/2J mice when given concurrently with LT, and this study demonstrates how the components of anthrax toxin can work together to increase lethality.
Journal ArticleDOI
Novel Common Integration Sites Targeted by Mouse Mammary Tumor Virus Insertion in Mammary Tumors Have Oncogenic Activity
TL;DR: It is shown here that expression of these three putative oncogenes in normal murine mammary gland cells altered their growth kinetics and caused their morphological transformation when grown in three dimensional cultures.
Journal ArticleDOI
Nasal immunization with a dual antigen anthrax vaccine induced strong mucosal and systemic immune responses against toxins and bacilli.
Brian R. Sloat,Zhengrong Cui +1 more
TL;DR: It is demonstrated that it is feasible to develop a novel dual-action nasal anthrax vaccine using a synthetic double-stranded RNA, polyriboinosinic-polyribocytidylic acid, as the adjuvant and the anti-PA antibody response was shown to have anthrax lethal toxin neutralization activity.
References
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Brad St. Croix,Carlo Rago,Carlo Rago,Victor E. Velculescu,Giovanni Traverso,Katharine E. Romans,Elizabeth A. Montgomery,Anita Lal,Gregory J. Riggins,Christoph Lengauer,Bert Vogelstein,Bert Vogelstein,Kenneth W. Kinzler +12 more
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Clonal selection and learning in the antibody system
TL;DR: A second selection process occurs during immune responses in which a new antibody repertoire is generated through somatic hypermutation, where only mutants binding antigen with high affinity survive to become memory cells.
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Vesicular stomatitis virus G glycoprotein pseudotyped retroviral vectors: concentration to very high titer and efficient gene transfer into mammalian and nonmammalian cells
TL;DR: The ability to concentrate vesicular stomatitis virus G glycoprotein pseudotyped vectors will facilitate gene therapy model studies and other gene transfer experiments that require direct delivery of vectors in vivo, and facilitate genetic studies in nonmammalian species, including the important zebrafish developmental system.
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Spermatogenic cells of the prepuberal mouse. Isolation and morphological characterization.
TL;DR: The successful isolation of these prepuberal cell types was accomplished by defining distinctive morphological characteristics of the cells and assessing the identity and purity of the isolated cell types by microscopy.