scholarly journals Transcriptional stimulation of anthrax toxin receptors by anthrax edema toxin and Bacillus anthracis Sterne spore

2007 ◽  
Vol 43 (1) ◽  
pp. 37-45 ◽  
Author(s):  
Qingfu Xu ◽  
Eric D. Hesek ◽  
Mingtao Zeng
Keyword(s):  
Bacillus Anthracis ◽  
Anthrax Toxin ◽  
Edema Toxin ◽  
Stimulation Of ◽  
Transcriptional Stimulation

scholarly journals A Review of the Efficacy of FDA-Approved B. anthracis Anti-Toxin Agents When Combined with Antibiotic or Hemodynamic Support in Infection- or Toxin-Challenged Preclinical Models

Toxins ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 53
Author(s):  
Zoe Couse ◽  
Xizhong Cui ◽  
Yan Li ◽  
Mahtab Moayeri ◽  
Stephen Leppla ◽  
...  
Keyword(s):  
Protective Antigen ◽  
Canine Model ◽  
Anthrax Toxin ◽  
Treated Animal ◽  
Preclinical Models ◽  
Hemodynamic Support ◽  
Fda Approval ◽  
Edema Toxin ◽  
Antibody Preparations ◽  
Insight Into

Anti-toxin agents for severe B. anthracis infection will only be effective if they add to the benefit of the two mainstays of septic shock management, antibiotic therapy and titrated hemodynamic support. Both of these standard therapies could negate benefits related to anti-toxin treatment. At present, three anthrax anti-toxin antibody preparations have received US Food and Drug Administration (FDA) approval: Raxibacumab, Anthrax Immune Globulin Intravenous (AIGIV) and ETI-204. Each agent is directed at the protective antigen component of lethal and edema toxin. All three agents were compared to placebo in antibiotic-treated animal models of live B. anthracis infection, and Raxibacumab and AIGIV were compared to placebo when combined with standard hemodynamic support in a 96 h canine model of anthrax toxin-associated shock. However, only AIG has actually been administered to a group of infected patients, and this experience was not controlled and offers little insight into the efficacy of the agents. To provide a broader view of the potential effectiveness of these agents, this review examines the controlled preclinical experience either in antibiotic-treated B. anthracis models or in titrated hemodynamic-supported toxin-challenged canines. The strength and weaknesses of these preclinical experiences are discussed.

scholarly journals Detection of Anthrax Toxin in the Serum of Animals Infected with Bacillus anthracis by Using Engineered Immunoassays

2006 ◽  
Vol 13 (6) ◽  
pp. 671-677 ◽  
Author(s):  
Robert Mabry ◽  
Kathleen Brasky ◽  
Robert Geiger ◽  
Ricardo Carrion ◽  
Gene B. Hubbard ◽  
...  
Keyword(s):  
Bacillus Anthracis ◽  
Protective Antigen ◽  
Lethal Factor ◽  
Systemic Circulation ◽  
Rapid Identification ◽  
Anthrax Toxin ◽  
Soluble Form ◽  
Before And After

ABSTRACT Several strategies that target anthrax toxin are being developed as therapies for infection by Bacillus anthracis. Although the action of the tripartite anthrax toxin has been extensively studied in vitro, relatively little is known about the presence of toxins during an infection in vivo. We developed a series of sensitive sandwich enzyme-linked immunosorbent assays (ELISAs) for detection of both the protective antigen (PA) and lethal factor (LF) components of the anthrax exotoxin in serum. The assays utilize as capture agents an engineered high-affinity antibody to PA, a soluble form of the extracellular domain of the anthrax toxin receptor (ANTXR2/CMG2), or PA itself. Sandwich immunoassays were used to detect and quantify PA and LF in animals infected with the Ames or Vollum strains of anthrax spores. PA and LF were detected before and after signs of toxemia were observed, with increasing levels reported in the late stages of the infection. These results represent the detection of free PA and LF by ELISA in the systemic circulation of two animal models exposed to either of the two fully virulent strains of anthrax. Simple anthrax toxin detection ELISAs could prove useful in the evaluation of potential therapies and possibly as a clinical diagnostic to complement other strategies for the rapid identification of B. anthracis infection.

Ligand-dependent, Pit-1/growth hormone factor-1 (GHF-1)-independent transcriptional stimulation of rat growth hormone gene expression by thyroid hormone receptors in vitro

1993 ◽  
Vol 13 (3) ◽  
pp. 1719-1727
Author(s):  
C S Suen ◽  
W W Chin
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Thyroid Hormone ◽  
Promoter Activity ◽  
Hormone Receptors ◽  
Nuclear Extract ◽  
In Vitro Transcription ◽  
Stimulation Of ◽  
Transcriptional Stimulation

The expression of the rat growth hormone (rGH) gene in the anterior pituitary gland is modulated by Pit-1/GHF-1, a pituitary-specific transcription factor, and by other more widely distributed factors, such as the thyroid hormone receptors (TRs), Sp1, and the glucocorticoid receptor. Thyroid hormone (T3)-mediated transcriptional stimulation of rGH gene expression has been extensively studied in vivo and in vitro including the measurements of (i) rGH mRNA by blot hybridization, (ii) transcriptional rate of rGH gene by nuclear run-on, and (iii) reporter gene expression in which a chimeric plasmid containing 5'-flanking sequences of the rGH gene linked to a reporter gene has been transfected either stably or transiently into pituitary and/or nonpituitary cells. From these studies, it has been suggested that the Pit-1/GHF-1 binding site is necessary for full T3 action. We developed a cell-free in vitro transcription system to examine further the roles of the TRs and Pit-1/GHF-1 in rGH gene activation. Using GH3 nuclear extract as a source of TRs and Pit-1/GHF-1, this in vitro transcription assay showed that T3 stimulation of rGH promoter activity is dependent on the addition of T3 to the GH3 nuclear extract. This transcriptional stimulation was augmented with increasing concentrations of ligand and was T3, but not T4 or reverse T3, specific. T3-mediated stimulation of rGH promoter activity was completely abolished by preincubation of the nuclear extract with rGH-thyroid hormone response element (-200 to -160) but not with Pit-1/GHF-1 (-137 to -65) oligonucleotides. Further, neither deletion of both Pit-1/GHF-1 binding sites nor mutation of the proximal Pit-1/GHF-1 binding site from the rGH promoter abrogated the T3 effect. These results provide evidence that T3-stimulated rGH promoter activity is independent of Pit-1/GHF-1 and raise the possibility that the stimulation of rGH gene expression by T3 might involve direct interaction of TRs with the general transcriptional apparatus.

decapentaplegic, a target gene of the wingless signalling pathway in the Drosophila midgut

Development ◽  
1996 ◽  
Vol 122 (3) ◽  
pp. 849-858 ◽  
Author(s):  
X. Yu ◽  
S. Hoppler ◽  
S. Eresh ◽  
M. Bienz
Keyword(s):  
Transcriptional Repression ◽  
Target Gene ◽  
Signalling Pathway ◽  
Homeotic Genes ◽  
Pathway Activity ◽  
Cell Groups ◽  
Signal Production ◽  
Stimulation Of ◽  
Transcriptional Stimulation

dishevelled, shaggy/zeste-white 3 and armadillo are required for transmission of the wingless signal in the Drosophila epidermis. We show that these genes act in the same epistatic order in the embryonic midgut to transmit the wingless signal. In addition to mediating transcriptional stimulation of the homeotic genes Ultrabithorax and labial, they are also required for transcriptional repression of labial by high wingless levels. Efficient labial expression thus only occurs within a window of intermediate wingless pathway activity. Finally, the shaggy/zeste-white 3 mutants revealed that wingless signalling can stimulate decapentaplegic transcription in the absence of Ultrabithorax, identifying decapentaplegic as a target gene of wingless. As decapentaplegic itself is required for wingless expression in the midgut, this represents a positive feed-back loop between two cell groups signalling to each other to stimulate each other's signal production.

scholarly journals Bacillus anthracis lethal toxin, but not edema toxin, increases pulmonary artery pressure and permeability in isolated perfused rat lungs

2019 ◽  
Vol 316 (5) ◽  
pp. H1076-H1090 ◽  
Author(s):  
Xizhong Cui ◽  
Wanying Xu ◽  
Pranita Neupane ◽  
Andie Weiser-Schlesinger ◽  
Ray Weng ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Bacillus Anthracis ◽  
Vascular Permeability ◽  
Pulmonary Artery Pressure ◽  
Lethal Toxin ◽  
Rat Lung ◽  
Fluid Accumulation ◽  
Pulmonary Vascular Permeability ◽  
Artery Pressure ◽  
Edema Toxin

Although lethal toxin (LT) and edema toxin (ET) contribute to lethality during Bacillus anthracis infection, whether they increase vascular permeability and the extravascular fluid accumulation characterizing this infection is unclear. We employed an isolated perfused Sprague-Dawley rat lung model to investigate LT and ET effects on pulmonary vascular permeability. Lungs ( n ≥ 6 per experimental group) were isolated, ventilated, suspended from a force transducer, and perfused. Lung weight and pulmonary artery (Ppa) and left atrial pressures were measured over 4 h, after which pulmonary capillary filtration coefficients (Kf.c) and lung wet-to-dry weight ratios (W/D) were determined. When compared with controls, LT increased Ppa over 4 h and Kf.c and W/D at 4 h ( P < 0.0001). ET decreased Ppa in a significant trend ( P = 0.09) but did not significantly alter Kf.c or W/D ( P ≥ 0.29). Edema toxin actually blocked LT increases in Ppa but not LT increases in Kf.c and W/D. When Ppa was maintained at control levels, LT still increased Kf.c and W/D ( P ≤ 0.004). Increasing the dose of each toxin five times significantly increased and a toxin-directed monoclonal antibody decreased the effects of each toxin ( P ≤ 0.05). Two rho-kinase inhibitors (GSK269962 and Y27632) decreased LT increases in Ppa ( P ≤ 0.02) but actually increased Kf.c and W/D in LT and control lungs ( P ≤ 0.05). A vascular endothelial growth factor receptor inhibitor (ZM323881) had no significant effect ( P ≥ 0.63) with LT. Thus, LT but not ET can increase pulmonary vascular permeability independent of increased Ppa and could contribute to pulmonary fluid accumulation during anthrax infection. However, pulmonary vascular dilation with ET could disrupt protective hypoxic vasoconstriction. NEW & NOTEWORTHY The most important findings from the present study are that Bacillus anthracis lethal toxin increases pulmonary artery pressure and pulmonary permeability independently in the isolated rat lung, whereas edema toxin decreases the former and does not increase permeability. Each effect could be a basis for organ dysfunction in patients with this lethal infection. These findings further support the need for adjunctive therapies that limit the effects of both toxins during infection.

scholarly journals Anthrax Toxin Detection: From In Vivo Studies to Diagnostic Applications

2020 ◽  
Vol 8 (8) ◽  
pp. 1103
Author(s):  
Jean-Nicolas Tournier ◽  
Clémence Rougeaux
Keyword(s):  
Animal Models ◽  
Bacillus Anthracis ◽  
Clinical Diagnosis ◽  
Anthrax Toxin ◽  
In Vivo Studies ◽  
Biochemical Methods ◽  
Highly Efficient ◽  
Anthrax Toxins ◽  
Diagnostic Applications

Anthrax toxins are produced by Bacillus anthracis throughout infection and shape the physiopathogenesis of the disease. They are produced in low quantities but are highly efficient. They have thus been long ignored, but recent biochemical methods have improved our knowledge in animal models. This article reviews the various methods that have been used and how they could be applied to clinical diagnosis.

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