Activated protein C ameliorates Bacillus anthracis lethal toxin-induced lethal pathogenesis in rats

Toxin-induced resistance in Bacillus anthracis lethal toxin-treated macrophages.

In the current study, we show that macrophages adaptively resist anthrax lethal toxin (LT) through a toxin-activated process termed toxin-induced resistance (TIR). TIR was triggered by pretreatment of RAW 264.7 or J774A.1 macrophages with a low dose of LT for at least 6 h, which resulted in resistance to high doses of LT for 96 h. Activation of TIR required functional toxin, because LT subunits...

Bacillus anthracis lethal toxin reduces human alveolar epithelial barrier function.

The lung is the site of entry for Bacillus anthracis in inhalation anthrax, the deadliest form of the disease. Bacillus anthracis produces virulence toxins required for disease. Alveolar macrophages were considered the primary target of the Bacillus anthracis virulence factor lethal toxin because lethal toxin inhibits mouse macrophages through cleavage of MEK signaling pathway components, but w...

Human Alveolar Epithelial Barrier Function Bacillus anthracis Lethal Toxin Reduces

Published Ahead of Print 1 October 2012. 2012, 80(12):4374. DOI: 10.1128/IAI.01011-12. Infect. Immun. Patrick Metcalf Burian, Jimmy Dale Ballard, Armin Braun and Jordan Mark Coggeshall, Shanjana Awasthi, Florea Lupu, Dennis Prenzler, Katherina Sewald, Daniel M. Williams, Kenneth Silasi-Mansat, Vijay Ramani, Tibor Zoltan Veres, Frauke Booth, Vineet Indrajit Patel, Ryan A. Zander, Robert Marybeth...

Lethal Toxin Bacillus anthracis to Resistance of Human Alveolar Macrophages

Role of the N-terminal amino acid of Bacillus anthracis lethal factor in lethal toxin cytotoxicity and its effect on the lethal toxin neutralization assay.

The cytotoxic activity of lethal factor (LF), a critical reagent used in the cell-based lethal toxin neutralization assay to assess anthrax vaccines, was shown to depend on the identity of its N-terminal amino acid, which plays a role in the targeting of LF to the proteasome for degradation. These results demonstrate that care must be taken to ensure that LF preparations used in standardized ce...