Anthrax Toxins

Moayeri, Mahtab; Leppla, Stephen H.

doi:10.1002/9780470891193.ch8

Cited by 5 publications

(9 citation statements)

References 263 publications

(346 reference statements)

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“…The three components of the anthrax exotoxins, PA, LF, and EF, are individually non-toxic, but they pair to form the two major virulence factors of B. anthracis : lethal toxin (LT, composed of LF + PA) and edema toxin (ET, composed of EF + PA) [8]. PA is the cellular binding moiety, and LF and EF are the catalytic moieties of the toxins.…”

Section: The Anthrax Toxin Components and Receptorsmentioning

confidence: 99%

“…These pathways play crucial roles in responses to a diverse array of stimuli, such as mitogens, proinflammatory cytokines, heat shock and a variety of cellular stresses. Therefore, LT causes a range of effects on cellular functions and is a major virulence factor of B. anthracis [8]. …”

Section: The Anthrax Toxin Components and Receptorsmentioning

confidence: 99%

“…These cells can be killed by LF in as little as 90 min [8]. Thus macrophages were initially thought to be the major target of LT in anthrax infection.…”

Section: The Anthrax Toxin Components and Receptorsmentioning

confidence: 99%

“…Experimental animals challenged with anthrax toxins manifest the symptoms shown in infected animals [8, 50]. Even though B. anthracis bacteria can be successfully eliminated by antibiotic treatment, the toxins released into circulation may still cause host death.…”

Section: Essential Roles Of Anthrax Toxins In Anthrax Infectionmentioning

confidence: 99%

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Anthrax lethal and edema toxins in anthrax pathogenesis

Liu¹,

Moayeri²,

Leppla³

2014

Trends in Microbiology

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181

189

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The pathophysiological effects resulting from many bacterial diseases are caused by exotoxins released by the bacteria. Bacillus anthracis, a spore-forming bacterium, is such a pathogen, causing anthrax through a combination of bacterial infection and toxemia. B. anthracis causes natural infection in humans and animals and has been a top bioterrorism concern since the 2001 anthrax attacks in the USA. The exotoxins secreted by B. anthracis use CMG2 as the major toxin receptor and play essential roles in pathogenesis during the entire course of the disease. This review focuses on the activities of anthrax toxins and their roles in initial and late stages of anthrax infection.

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Section: The Anthrax Toxin Components and Receptorsmentioning

confidence: 99%

Section: The Anthrax Toxin Components and Receptorsmentioning

confidence: 99%

“…These cells can be killed by LF in as little as 90 min [8]. Thus macrophages were initially thought to be the major target of LT in anthrax infection.…”

Section: The Anthrax Toxin Components and Receptorsmentioning

confidence: 99%

Section: Essential Roles Of Anthrax Toxins In Anthrax Infectionmentioning

confidence: 99%

See 2 more Smart Citations

Anthrax lethal and edema toxins in anthrax pathogenesis

Liu¹,

Moayeri²,

Leppla³

2014

Trends in Microbiology

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181

189

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“…LT can also induce anergy in Type I CD1d-restricted natural killer T (NKT) cells [218]. DCs, T, and B cells are also affected by exotoxins, though as mentioned in a previous review, it is not certain what role this plays given that anthrax is an acute disease and there is evidence that survivors have long lasting immunity [39,219]. It is possible that DCs, T, and B cells increase the activation and bacteriocidal activity of the innate immune system indirectly through cytokine and chemokine production.…”

Section: Immunological Effectsmentioning

confidence: 99%

Opening moves: early events in anthrax pathogenesis and their consequences for dissemination

Lowe

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Bacillus anthracis is a Gram positive sporulating bacterium that is the causative agent of anthrax. Early steps in dissemination are understudied due to the asymptomatic and asynchronous nature of B. anthracis infections. The goals of these studies are to establish a model of the early steps of B. anthracis infections and examine how the initial site of infection and exotoxin production affect bacterial dissemination. In these studies, a mouse model was used in combination with a bioluminescent signature tagged library to determine how B.anthracis disseminates through the host and the roles of an exotoxin component, lethal factor, in colonization and dissemination. This library allowed for real time observation of dissemination and analysis of bacterial population dynamics. In the first set of experiments, mice were infected via inhalational or subcutaneous routes with the tagged library to determine how the bacterial population changed during dissemination. In inhalational and subcutaneous infections, the disseminated population was comprised of a small subset of the original library.This indicated the presence of a population bottleneck, a random decrease in genetic diversity during the infection. Surprisingly, the diminishment and location of the bottleneck varied depending on the initial site of infection. This suggested B. anthracis exploits multiple host environments and some sites may be more permissive for dissemination than others. In the second set of experiments, mice were infected with a signature tagged library where a portion of clones lacked lethal factor. Lethal factor is known to be an important virulence factor as deletion results in attenuated or complete loss of virulence in most animal models. Host survival increased when < 10% of the library produced lethal factor, but few other differences were observed. Furthermore, decreases in the proportion of lethal factor producing clones led to fewer clones disseminating. These findings suggest that a threshold of lethal factor must be ii produced for colonization and dissemination to occur in vivo. In total, this work provides an understanding of how B. anthracis is able to rapidly disseminate from a several tissues and gives insights in where future therapeutics should be focused to reduce disease incidence.iii

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Lipoprotein biosynthesis by prolipoprotein diacylglyceryl transferase is required for efficient spore germination and full virulence of Bacillus anthracis

Okugawa

Moayeri

Pomerantsev

et al. 2011

Molecular Microbiology

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Bacterial lipoproteins play a crucial role in virulence in some Gram-positive bacteria. However, the role of lipoprotein biosynthesis in Bacillus anthracis is unknown. We created a B. anthracis mutant strain altered in lipoproteins by deleting the lgt gene encoding the enzyme prolipoprotein diacylglyceryl transferase, which attaches the lipid anchor to prolipoproteins. 14C-palmitate labeling confirmed that the mutant strain lacked lipoproteins, and hydrocarbon partitioning showed it to have decreased surface hydrophobicity. The anthrax toxin proteins were secreted from the mutant strain at nearly the same levels as from the wild-type strain. The TLR2-dependent TNF-α response of macrophages to heat-killed lgt mutant bacteria was reduced. Spores of the lgt mutant germinated inefficiently in vitro and in mouse skin. As a result, in a murine subcutaneous infection model, lgt mutant spores had markedly attenuated virulence. In contrast, vegetative cells of the lgt mutant were as virulent as those of the wild-type strain. Thus, lipoprotein biosynthesis in B. anthracis is required for full virulence in a murine infection model.

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Anthrax Toxins

Cited by 5 publications

References 263 publications

Anthrax lethal and edema toxins in anthrax pathogenesis

Anthrax lethal and edema toxins in anthrax pathogenesis

Opening moves: early events in anthrax pathogenesis and their consequences for dissemination

Lipoprotein biosynthesis by prolipoprotein diacylglyceryl transferase is required for efficient spore germination and full virulence of Bacillus anthracis

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