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Pathogen Page

Bacillus anthracis

I. General Information

1. NCBI Taxonomy ID:

2. Disease:

Anthrax

3. Introduction

The pathology of anthrax is almost entirely mediated by expression of two secreted toxins: lethal toxin (LeTx) and edema toxin (EdTx). The natural form of anthrax is extremely rare in the United States, with only 244 cases reported between 1944 and 1999. Natural infection of humans occurs through direct exposure to spores from infected animals or their products, such as hides or wool. Anthrax is primarily a disease of animals and is probably propagated in the environment through spores present in soil at sites of infected carcasses. The causative agent of anthrax is B. anthracis, which produces transmissible and infectious spores. The vegetative anthrax bacillus is not readily transmissible, but the spores are environmentally robust for years and can be easily transmitted to humans. This phenomenon is the core of anthrax biowarfare and bioterrorism concern, since infective spores can be obtained from fermentation cultures and purified in large quantities in a pure non-aggregable form suitable for aerosol dissemination. This could potentially result in the intentional dissemination of spores to cause human infection (Brey, 2005).

4. Microbial Pathogenesis

In general, spores are phagocytosed by macrophages and germinate within phagolysosomes. Vegetative bacteria release many toxins leading to macrophage death. Lethal toxin acts on host macrophages and induces the release of proinflammatory cytokines responsible for inducing sudden and fatal shock (Hanna et al., 1999). Edema toxin causes localized edema and systemic shock (Hirsh et al, 2004). Other virulence factors allow for survival within phagolysosomes and on mucosal surfaces (Inh and MprF), escape from phagolysosomes and phagocytic cells (anthrolysins), iron acquiring products (Dlp), and regulation of cellular products (AtxA and AcpA) (Hirsh et al, 2004).

Link to pathogenesis of Bacillus anthracis in HazARD.

5. Host Ranges and Animal Models

Host ranges include the following: livestock or other herbivores (eg, cattle, sheep, goats, pigs, bison, water buffalo) acquire infection by consuming contaminated soil or feed; spores are infectious agents that can enter the human body through skin lesions, ingestion, or inhalation; and laboratory animal models include Guinea pigs, Syrian hamsters, and various mouse models (PathPort).

6. Host Protective Immunity

Since protection against anthrax is induced by vaccines containing PA as the major immunogen, with minor amounts of EF and LF, antibodies against PA and other toxin components are essential in the protection against anthrax. Serum therapy has been used in the past for the treatment of human anthrax with some success. PA is a key immunogen for antianthrax vaccine development since it induces the production of toxin-neutralizing Abs. However, vital, anti-PA Abs are not the only, or completely sufficient, means for an immune host to impede the development of anthrax (Glomski et al., 2007). Immune serum containing antibodies to PA can be effective in the therapy of established experimental infection in guinea pigs. However, The identification of anti-toxic immunity as the most important means for protection against B. anthracis has been complicated by lack of an entirely well-accepted animal model for evaluating immunity to LeTx and to spores of different anthrax isolates, due to varying susceptibility of animal models to spores of different origin (Brey, 2005).

Anti-capsule antibodies may also be important in controlling the outgrowth phase of anthrax infection, since they would be presumed to fix complement and kill vegetative cells. However, antibodies to the poly γ-d-glutamate capsule have not been well studied, because the capsule is poorly immunogenic and is a T cell-independent antigen. Recently, a series of murine monoclonal antibodies to the capsule has been obtained by immunizing mice with an anthrax capsule isoform isolated from B. licheniformis. The capsule is a major virulence factor in mice. Although there is a definitive role for anti-toxin antibodies in protection against anthrax, it is not yet clear what levels of antibodies will be required to protect humans against anthrax after vaccination or passive injection of protective antibodies. This consideration is important since challenge studies cannot be performed in humans, and correlates of immunity have to be extrapolated from animal studies (Brey, 2005).

Humoral immunity does not protect from nontoxinogenic capsulated bacteria; however, a cellular immune response by IFN-{gamma}-producing CD4 T lymphocytes protect mice. These results provide evidence of protective cellular immunity against capsulated B. anthracis and suggest that future antianthrax vaccines should strive to augment cellular adaptive immunity (Glomski et al., 2007).

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