Anthrax toxins: A weapon to systematically dismantle the host immune defenses

Tournier, Jean‐Nicolas; Paccani, Silvia Rossi; Quesnel‐Hellmann, Anne; Baldari, Cosima T.

doi:10.1016/j.mam.2009.06.002

Cited by 116 publications

(127 citation statements)

References 90 publications

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“…The most prominent effect of LT on macrophages is the induction of cell death (27,34,35). The LF present in LT cleaves and inactivates MAPKK1, MAPKK2, MAPKK3, MAPKK4, and MAPKK6, each of which plays an important role in MAPK-dependent immune activation, and the inactivation of the MAPKKs results in impaired host defenses (27,34,35).…”

Section: Resultsmentioning

confidence: 99%

The Poly-γ- d -Glutamic Acid Capsule of Bacillus anthracis Enhances Lethal Toxin Activity

et al. 2011

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The poly-␥-D-glutamic acid (PGA) capsule is one of the major virulence factors of Bacillus anthracis, which causes a highly lethal infectious disease. The PGA capsule disguises B. anthracis from immune surveillance and allows its unimpeded growth in the host. The PGA capsule recently was reported to be associated with lethal toxin (LT) in the blood of experimentally infected animals (M. H. Cho, et al., Infect. Immun. 78:387-392, 2010). The effect of PGA, either alone or in combination with LT, on macrophages, which play an important role in the progression of anthrax disease, has not been thoroughly investigated. In this study, we investigated the effect of PGA on LT cytotoxicity using the mouse macrophage cell line J774A.1. PGA produced a concentrationdependent enhancement of the cytotoxicity of LT on J774A.1 cells through an enhancement in the binding and accumulation of protective antigen to its receptors. The increase of LT activity was confirmed using Western blot analysis, which showed that the combination of PGA and LT produced a greater degree of degradation of mitogen-activated protein kinase kinases and an increased level of the activation of the proform of caspase-1 to its processed form compared to the effects of LT alone. In addition, mice that received a tail vein injection of both PGA and LT had a significantly increased rate of death compared to that of mice injected with LT alone. PGA had no effect when added to cultures or administered to mice in the absence of LT. These results emphasize the importance of PGA in the pathogenesis of anthrax infection.

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Section: Resultsmentioning

confidence: 99%

The Poly-γ- d -Glutamic Acid Capsule of Bacillus anthracis Enhances Lethal Toxin Activity

et al. 2011

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“…The most lethal form of the disease, inhalational anthrax, occurs when inhaled spores are phagocytosed by resident macrophages or dendritic cells and are carried to regional lymph nodes (1). En route, the bacteria germinate, escape the phagolysosome, and break out of the cell to replicate extracellularly, eventually leading to massive septicemia, shock, and death (2).…”

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confidence: 99%

Novel Role for the yceGH Tellurite Resistance Genes in the Pathogenesis of Bacillus anthracis

et al. 2014

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Bacillus anthracis, the causative agent of anthrax, relies on multiple virulence factors to subvert the host immune defense. Using Caenorhabditis elegans as an infection model, we screened approximately 5,000 transposon mutants of B. anthracis Sterne for decreased virulence. One of the attenuated mutants resulted in loss of expression of yceG and yceH, the last two genes in a sixgene cluster of tellurite resistance genes. We generated an analogous insertional mutant to confirm the phenotype and characterize the role of yceGH in resistance to host defenses. Loss of yceGH rendered the mutants more sensitive to tellurite toxicity as well as to host defenses such as reactive oxygen species and the cathelicidin family of antimicrobial peptides. Additionally, we see decreased survival in mammalian models of infection, including human whole blood and in mice. We identify a novel role for the yceGH genes in B. anthracis Sterne virulence and suggest that C. elegans is a useful infection model to study anthrax pathogenesis.

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“…3 The toxins modulate host immune responses leading to immune paralysis. 4,5 The mouse model has been, and still is, extensively used and has allowed significant advances in the understanding of key steps of anthrax. Using bioluminescent imaging, we recently followed in real time the kinetics and dissemination pattern of encapsulated nontoxinogenic or nonencapsulated toxinogenic B. anthracis during murine cutaneous, inhalational, and gastrointestinal infections.…”

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confidence: 99%

Noninvasive Imaging Technologies Reveal Edema Toxin as a Key Virulence Factor in Anthrax

Dumetz

Jouvion

Khun

et al. 2011

The American Journal of Pathology

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Powerful noninvasive imaging technologies enable realtime tracking of pathogen-host interactions in vivo, giving access to previously elusive events. We visualized the interactions between wild-type Bacillus anthracis and its host during a spore infection through bioluminescence imaging coupled with histology. We show that edema toxin plays a central role in virulence in guinea pigs and during inhalational infection in mice. Edema toxin (ET), but not lethal toxin (LT), markedly modified the patterns of bacterial dissemination leading, to apparent direct dissemination to the spleen and provoking apoptosis of lymphoid cells. Each toxin alone provoked particular histological lesions in the spleen. When ET and LT are produced together during infection, a specific temporal pattern of lesion developed, with early lesions typical of LT, followed at a later stage by lesions typical of ET. Our study provides new insights into the complex spatial and temporal effects of B. anthracis toxins in the infected host, suggesting a greater role than previously suspected for ET in anthrax and suggesting that therapeutic targeting of ET contributes to protection.

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Anthrax toxins: A weapon to systematically dismantle the host immune defenses

Cited by 116 publications

References 90 publications

The Poly-γ- d -Glutamic Acid Capsule of Bacillus anthracis Enhances Lethal Toxin Activity

The Poly-γ- d -Glutamic Acid Capsule of Bacillus anthracis Enhances Lethal Toxin Activity

Novel Role for the yceGH Tellurite Resistance Genes in the Pathogenesis of Bacillus anthracis

Noninvasive Imaging Technologies Reveal Edema Toxin as a Key Virulence Factor in Anthrax

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