Anthrax toxin channel: What we know based on over 30 years of research

Liu, Wenxing; Nestorovich, Ekaterina M.

doi:10.1016/j.bbamem.2021.183715

Cited by 7 publications

(2 citation statements)

References 210 publications

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“…Lethal factor is a metalloprotease that catalyzes the cleavage of the mitogen-activated protein kinase kinase (MAPKK) and Nlrp1, thereby influencing inflammasome formation. Edema factor enhances the amount of intracellular cAMP by acting as adenylyl cyclase (for review see [24]). Biochemical and structural analysis of anthrax toxin led to the identification of the domains of EF and LF that are essential for PA binding.…”

Section: Toxins Forming Pores For Delivery Of An Enzymementioning

confidence: 99%

Some Examples of Bacterial Toxins as Tools

Schmidt

2024

Toxins

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Pathogenic bacteria produce diverse protein toxins to disturb the host’s defenses. This includes the opening of epithelial barriers to establish bacterial growth in deeper tissues of the host and to modulate immune cell functions. To achieve this, many toxins share the ability to enter mammalian cells, where they catalyze the modification of cellular proteins. The enzymatic activity is diverse and ranges from ribosyl- or glycosyl-transferase activity, the deamidation of proteins, and adenylate-cyclase activity to proteolytic cleavage. Protein toxins are highly active enzymes often with tight specificity for an intracellular protein or a protein family coupled with the intrinsic capability of entering mammalian cells. A broad understanding of their molecular mechanisms established bacterial toxins as powerful tools for cell biology. Both the enzymatic part and the pore-forming/protein transport capacity are currently used as tools engineered to study signaling pathways or to transport cargo like labeled compounds, nucleic acids, peptides, or proteins directly into the cytosol. Using several representative examples, this review is intended to provide a short overview of the state of the art in the use of bacterial toxins or parts thereof as tools.

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Section: Toxins Forming Pores For Delivery Of An Enzymementioning

confidence: 99%

Some Examples of Bacterial Toxins as Tools

Schmidt

2024

Toxins

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“…The attacks caused life-threatening infections in 11 patients, 5 of whom succumbed [ 9 , 10 , 11 ]. Disease pathology is mediated by the pXO1 virulence plasmid of B. anthracis , which expresses the anthrax toxin components, including protective antigen (PA) and two enzymatic moieties, edema factor (EF) and lethal factor (LF) [ 1 , 12 , 13 ]. The PA toxin component is an 83-kDa protein with four functional domains [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Development of a New Cell-Based AP-1 Gene Reporter Potency Assay for Anti-Anthrax Toxin Therapeutics

Ouyang,

Xie,

Fang

et al. 2023

Toxins

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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.

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Anthrax Toxin: Model System for Studying Protein Translocation

Krantz

2024

Journal of Molecular Biology

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Anthrax toxin channel: What we know based on over 30 years of research

Cited by 7 publications

References 210 publications

Some Examples of Bacterial Toxins as Tools

Some Examples of Bacterial Toxins as Tools

Development of a New Cell-Based AP-1 Gene Reporter Potency Assay for Anti-Anthrax Toxin Therapeutics

Anthrax Toxin: Model System for Studying Protein Translocation

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