Neurologic Complications of Anthrax

Meyer, Michaël

doi:10.1001/archneur.60.4.483

Cited by 29 publications

(16 citation statements)

References 24 publications

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“…In clinical studies, hemorrhage occurs in the draining lymph nodes, bowel segments, and meninges. 11,44,45 In animal models, hemorrhage was observed in mediastinal, mesenteric, and tracheobronchial lymph nodes, as well as in the meninges, lungs, and small intestinal serosas of B. anthracis-infected animals. 11 Because LT treatments induce hemorrhage, 14,46 these results might indicate that anthrax LT is involved in the hemorrhagic pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Acquired coagulant factor VIII deficiency induced byBacillus anthracislethal toxin in mice

Sun¹,

Lee

Kau

et al. 2015

Virulence

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(2015) Acquired coagulant factor VIII deficiency induced by Bacillus anthracis lethal toxin in mice, Virulence, 6:5, 466-475, DOI: 10.1080/21505594.2015 Keywords: Anthrax, coagulation factor VIII, hemorrhage, lethal toxinMice treated with anthrax lethal toxin (LT) exhibit hemorrhage caused by unknown mechanisms. Moreover, LT treatment in mice induced liver damage. In this study, we hypothesized that a suppressed coagulation function may be associated with liver damage, because the liver is the major producing source of coagulation factors. The hepatic expression of coagulant factors and the survival rates were analyzed after cultured cells or mice were exposed to LT. In agreement with our hypothesis, LT induces cytotoxicity against hepatic cells in vitro. In addition, suppressed expression of coagulation factor VIII (FVIII) in the liver is associated with a prolonged plasma clotting time in LT-treated mice, suggesting a suppressive role of LT in coagulation. Accordingly, we further hypothesized that a loss-of-function approach involving treatments of an anticoagulant should exacerbate LT-induced abnormalities, whereas a gain-offunction approach involving injections of recombinant FVIII to complement the coagulation deficiency should ameliorate the pathogenesis. As expected, a sublethal dose of LT caused mortality in the mice that were non-lethally pretreated with an anticoagulant (warfarin). By contrast, treatments of recombinant FVIII reduced the mortality from a lethal dose of LT in mice. Our results indicated that LT-induced deficiency of FVIII is involved in LT-mediated pathogenesis. Using recombinant FVIII to correct the coagulant defect may enable developing a new strategy to treat anthrax.

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Section: Discussionmentioning

confidence: 99%

Acquired coagulant factor VIII deficiency induced byBacillus anthracislethal toxin in mice

Sun¹,

Lee

Kau

et al. 2015

Virulence

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“…Also CSF from lumbar puncture was positive for B. anthracis DNA by PCR Growth of the anthrax bacilli in CSF cultures is accepted as gold standard but it can take time (3). The major neurological complication of anthrax meningoencephalitis is mortal subarachnoid hemorrhages (5)(6)(7)(9)(10)(11). In the literature, the most common histopathological findings of anthrax meningoencephalitis are necrotizing vasculitis, cerebral infarction, edema, hemorrhagic meningitis, intraventricular hemorrhage, multifocal subarachnoid or intraparenchymal hemorrhages (3).…”

Section: Discussionmentioning

confidence: 99%

CT and MRI Findings of Anthrax Meningoencephalitis; Case Report

Özkaçmaz¹

2017

Eastern J Med

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“…Anthrax meningitis/meningoencephalitis is the main neurological complication of anthrax infection and is associated with extremely high mortality despite antimicrobial therapy and supportive care (24,27). We have previously shown that B. anthracis Sterne is capable of invading brain endothelium in a process involving host actin cytoskeleton rearrangement to facilitate CNS entry (44); however, the basic pathogenic mechanisms by which B. anthracis penetrates the BBB have not been described.…”

Section: Discussionmentioning

confidence: 99%

“…Here, the spores germinate into vegetative bacteria, multiply, and then disseminate throughout the host, causing septicemia and toxemia (8). Systemic disease can be complicated by the onset of a fulminant and rapidly fatal hemorrhagic meningitis and meningoencephalitis (27). Anthrax meningitis is associated with a high mortality rate despite intensive antibiotic therapy (24).…”

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confidence: 99%

Penetration of the Blood-Brain Barrier by Bacillus anthracis Requires the pXO1-Encoded BslA Protein

et al. 2009

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Anthrax is a zoonotic disease caused by the gram-positive spore-forming bacterium Bacillus anthracis. Human infection occurs after the ingestion, inhalation, or cutaneous inoculation of B. anthracis spores. The subsequent progression of the disease is largely mediated by two native virulence plasmids, pXO1 and pXO2, and is characterized by septicemia, toxemia, and meningitis. In order to produce meningitis, blood-borne bacteria must interact with and breach the blood-brain barrier (BBB) that is composed of a specialized layer of brain microvascular endothelial cells (BMEC). We have recently shown that B. anthracis Sterne is capable of penetrating the BBB in vitro and in vivo, establishing the classic signs of meningitis; however, the molecular mechanisms underlying the central nervous system (CNS) tropism are not known. Here, we show that attachment to and invasion of human BMEC by B. anthracis Sterne is mediated by the pXO1 plasmid and an encoded envelope factor, BslA. The results of studies using complementation analysis, recombinant BslA protein, and heterologous expression demonstrate that BslA is both necessary and sufficient to promote adherence to brain endothelium. Furthermore, mice injected with the BslA-deficient strain exhibited a significant decrease in the frequency of brain infection compared to mice injected with the parental strain. In addition, BslA contributed to BBB breakdown by disrupting tight junction protein ZO-1. Our results identify the pXO1-encoded BslA adhesin as a critical mediator of CNS entry and offer new insights into the pathogenesis of anthrax meningitis.

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Neurologic Complications of Anthrax

Cited by 29 publications

References 24 publications

Acquired coagulant factor VIII deficiency induced byBacillus anthracislethal toxin in mice

Acquired coagulant factor VIII deficiency induced byBacillus anthracislethal toxin in mice

CT and MRI Findings of Anthrax Meningoencephalitis; Case Report

Penetration of the Blood-Brain Barrier by Bacillus anthracis Requires the pXO1-Encoded BslA Protein

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