Bacillus anthracis

About: Bacillus anthracis is a research topic. Over the lifetime, 3994 publications have been published within this topic receiving 128122 citations.

Studies on a lysogenic Bacillus strain. I. A Bacteriophage specific for Bacillus anthracis

Abstract: A bacteriophage is described which attacks almost exclusively strains of Bacillus anthracis, and attacks all the strains of this species which have been tested.As well as attacking typical strains of this species it attacks atypical variants.Strains of B. anthracis are not attacked by this phage when they are in a muciod state.A few strains of B. anthracis are only feebly attacked by this phage. Some experiments, conducted in an attempt to discover the reason for this, are described.The results are discussed and arguments in favour of regarding B. anthracis as a valid species are put forward.

A monoclonal antibody to Bacillus anthracis protective antigen defines a neutralizing epitope in domain 1.

Abstract: Antibody (Ab) responses to Bacillus anthracis toxins are protective, but relatively few protective monoclonal antibodies (MAbs) have been reported. Protective antigen (PA) is essential for the action of B. anthracis lethal toxin (LeTx) and edema toxin. In this study, we generated two MAbs to PA, MAbs 7.5G and 10F4. These MAbs did not compete for binding to PA, consistent with specificities for different epitopes. The MAbs were tested for their ability to protect a monolayer of cultured macrophages against toxin-mediated cytotoxicity. MAb 7.5G, the most-neutralizing MAb, bound to domain 1 of PA and reduced LeTx toxicity in BALB/c mice. Remarkably, MAb 7.5G provided protection without blocking the binding of PA or lethal factor or the formation of the PA heptamer complex. However, MAb 7.5G slowed the proteolytic digestion of PA by furin in vitro, suggesting a potential mechanism for Ab-mediated protection. These observations indicate that some Abs to domain 1 can contribute to host protection.

Murine aerosol challenge model of anthrax.

Abstract: The availability of relevant and useful animal models is critical for progress in the development of effective vaccines and therapeutics. The infection of rabbits and non-human primates with fully virulent Bacillus anthracis spores provides two excellent models of anthrax disease. However, the high cost of procuring and housing these animals and the specialized facilities required to deliver fully virulent spores limit their practical use in early stages of product development. Conversely, the small size and low cost associated with using mice makes this animal model more practical for conducting experiments in which large numbers of animals are required. In addition, the availability of knockout strains and well-characterized immunological reagents makes it possible to perform studies in mice that cannot be performed easily in other species. Although we, along with others, have used the mouse aerosol challenge model to examine the outcome of B. anthracis infection, a detailed characterization of the disease is lacking. The current study utilizes a murine aerosol challenge model to investigate disease progression, innate cytokine responses, and histological changes during the course of anthrax after challenge with aerosolized spores. Our results show that anthrax disease progression in a complement-deficient mouse after challenge with aerosolized Sterne spores is similar to that described for other species, including rabbits and non-human primates, challenged with fully virulent B. anthracis. Thus, the murine aerosol challenge model is both useful and relevant and provides a means to further investigate the host response and mechanisms of B. anthracis pathogenesis.

Resident CD11c+ Lung Cells Are Impaired by Anthrax Toxins after Spore Infection

Abstract: Bacillus anthracis secretes 2 toxins: lethal toxin (LT) and edema toxin (ET). We investigated their role in the physiopathologic mechanisms of inhalational anthrax by evaluating murine lung dendritic cell (LDC) functions after infection with B. anthracis strains secreting LT, ET, or both or with a nontoxinogenic strain. Three lung cell populations gated on CD11c/CD11b expression were obtained after lung digestion: (1) CD11c high /CD11b low (alveolar macrophages), (2) CD11c intermediate (int) /CD11b int (LDCs), and (3) CD11c low /CD11b high (interstitial macrophages or monocytes). After infection with LT-secreting strains, a decrease in costimulatory molecule expression on LDCs was observed. All CD11c + cells infected with a nontoxinogenic strain secreted tumor necrosis factor (TNF)–a, interleukin (IL)–10, and IL-6. LT-secreting strains inhibited overall cytokine secretion, whereas the ET-secreting strain inhibited only TNF-a secretion and increased IL-6 secretion. Similar results were obtained after preincubation with purified toxins. Our results suggest that anthrax toxins secreted during infection impair LDC function and suppress the innate immune response.

Immune system paralysis by anthrax lethal toxin: the roles of innate and adaptive immunity.

Abstract: Summary Since the deliberate use of anthrax as a bioweapon in the USA in 2001, an enormous amount of attention has been focused on the biology of Bacillus anthracis , the causative bacterium of anthrax. Fatal systemic anthrax involves massive bacteraemia and toxaemia with non-descript early symptoms until the onset of shock and sudden death. The outbreak of fatal symptoms after the incubation period of B anthracis suggests an impairment of the host immune system against this pathogen. Thus, it is likely that B anthracis will posess certain strategies to escape from the host immune system. However, the mechanisms of such immune-evasion strategies are not fully characterised yet. Given the critical role of B anthracis toxins in anthrax pathogenesis, much effort has been made to understand the pathological nature of the toxins. Recent studies have shown the pleiotropic actions of anthrax lethal toxin on host innate immune cells, and that several effects of anthrax lethal toxin may directly account for the mechanism of immune intervention by B anthracis .