Bacillus anthracis Toxins

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Bacterial Toxins".

Deadline for manuscript submissions: closed (18 August 2023) | Viewed by 1327

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Guest Editor
Division of Biotechnology Review and Research II, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA
Interests: Bacillus anthracis toxins

Special Issue Information

Dear Colleagues,

Anthrax is a life-threatening disease caused by an infection with Bacillus anthracis. The pXO1 virulence plasmid of B. anthracis expresses a binary anthrax toxin comprising a protective antigen (PA) and two enzymatic moieties, edema factor (EF) and lethal factor (LF). PA binds surface receptors on the host cells, mediating the translocation of the enzymatic moieties into the cytoplasm of the host cells. LF disrupts critical cellular signaling pathways via its zinc-dependent metalloprotease activity, which specifically cleaves mitogen-activated protein kinases, NACHT leucine-rich repeat protein 1 (NLRP1) and the regulatory subunits of phosphoinositide-3 kinase. EF is a Ca2+ and calmodulin-dependent adenylate cyclase that increases the level of cAMP in the host cell, disrupting water homeostasis, intracellular signaling pathways and macrophage function. This Special Issue of Toxins aims to provide a scientific platform for scientists performing fundamental, applied and translational research related to the Bacillus anthracis toxins. This Special Issue will include original studies, reviews and method papers on all research areas of the Bacillus anthracis toxins.

Dr. Weiming Ouyang
Guest Editor

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Keywords

  • anthrax
  • lethal toxin
  • edema toxin
  • MAPK
  • MKK
  • NLRP1
  • PI-3K

Published Papers (1 paper)

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Research

13 pages, 1224 KiB  
Article
Development of a New Cell-Based AP-1 Gene Reporter Potency Assay for Anti-Anthrax Toxin Therapeutics
by Weiming Ouyang, Tao Xie, Hui Fang and David M. Frucht
Toxins 2023, 15(9), 528; https://doi.org/10.3390/toxins15090528 - 28 Aug 2023
Viewed by 1074
Abstract
Anthrax toxin is a critical virulence factor of Bacillus anthracis. The toxin comprises protective antigen (PA) and two enzymatic moieties, edema factor (EF) and lethal factor (LF), forming bipartite lethal toxin (LT) and edema toxin (ET). PA binds cellular surface receptors and [...] Read more.
Anthrax toxin is a critical virulence factor of Bacillus anthracis. The toxin comprises protective antigen (PA) and two enzymatic moieties, edema factor (EF) and lethal factor (LF), forming bipartite lethal toxin (LT) and edema toxin (ET). PA binds cellular surface receptors and is required for intracellular translocation of the enzymatic moieties. For this reason, anti-PA antibodies have been developed as therapeutics for prophylaxis and treatment of human anthrax infection. Assays described publicly for the control of anti-PA antibody potency quantify inhibition of LT-mediated cell death or the ET-induced increase in c-AMP levels. These assays do not fully reflect and/or capture the pathological functions of anthrax toxin in humans. Herein, we report the development of a cell-based gene reporter potency assay for anti-PA antibodies based on the rapid LT-induced degradation of c-Jun protein, a pathogenic effect that occurs in human cells. This new assay was developed by transducing Hepa1c1c7 cells with an AP-1 reporter lentiviral construct and has been qualified for specificity, accuracy, repeatability, intermediate precision, and linearity. This assay not only serves as a bioassay for LT activity, but has applications for characterization and quality control of anti-PA therapeutic antibodies or other products that target the AP-1 signaling pathway. Full article
(This article belongs to the Special Issue Bacillus anthracis Toxins)
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